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Barrier Enhancing Signals in Pulmonary Edema

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Abstract

Increased endothelial permeability and reduction of alveolar liquid clearance capacity are two leading pathogenic mechanisms of pulmonary edema, which is a major complication of acute lung injury, severe pneumonia, and acute respiratory distress syndrome, the pathologies characterized by unacceptably high rates of morbidity and mortality. Besides the success in protective ventilation strategies, no efficient pharmacological approaches exist to treat this devastating condition. Understanding of fundamental mechanisms involved in regulation of endothelial permeability is essential for development of barrier protective therapeutic strategies. Ongoing studies characterized specific barrier protective mechanisms and identified intracellular targets directly involved in regulation of endothelial permeability. Growing evidence suggests that, although each protective agonist triggers a unique pattern of signaling pathways, selected common mechanisms contributing to endothelial barrier protection may be shared by different barrier protective agents. Therefore, understanding of basic barrier protective mechanisms in pulmonary endothelium is essential for selection of optimal treatment of pulmonary edema of different etiology. This article focuses on mechanisms of lung vascular permeability, reviews major intracellular signaling cascades involved in endothelial monolayer barrier preservation and summarizes a current knowledge regarding recently identified compounds which either reduce pulmonary endothelial barrier disruption and hyperpermeability, or reverse preexisting lung vascular barrier compromise induced by pathologic insults. © 2013 American Physiological Society. Compr Physiol 3:429‐484, 2013.

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Figure 1. Figure 1.

Classification of pulmonary edema.

Figure 2. Figure 2.

Role of Cdc42, Rac, and Rho GTPases in actin cytoskeletal remodeling.

Figure 3. Figure 3.

Regulation of endothelial permeability by microtubule‐dependent signaling. Stable microtubules destabilization by microtubule toxins, bacterial endotoxin, cytokines, or edemagenic agonists (thrombin) causes release of Rho‐specific guanine nucleotide exchange factor GEF‐H1 leading to activation of Rho signaling, actin cytoskeletal remodeling, actomyosin contraction and endothelial permeability. Activation of GEF‐H1 may be inhibited by stabilization of microtubule or activation of Rac and its effector p21‐activated kinase 1 (PAK‐1).

Figure 4. Figure 4.

Schematic representation of focal adhesion protein complex linked via αβ‐integrin heterodimers to the extracellular matrix and via α‐actinin and vinculin linker proteins to the actin cytoskeleton.

Figure 5. Figure 5.

Scheme of adherens junction complex. Cell‐cell contacts are formed by homotypic interactions of transmembrane protein VE‐cadherin, which interacts with αβγ‐catenin complex and p120‐catenin via intracellular domains. Anchorage of adherens junctions to actin cytoskeleton is primarily controlled by α‐catenin and α‐actinin, but may also involve vinculin and ZO proteins. Interaction of Rac/Cdc42 effector IQRas GTPase‐activating protein 1 with either actin cytoskeleton, or beta‐catenin is regulated by Rac/Cdc42 activities and may represent a Rac/Cdc42‐dependent mechanism regulating adherens junction assembly and endothelial barrier.

Figure 6. Figure 6.

Structure of tight junction complex. Extracellular domains of claudin, occluding, or junctional adhesion molecule (JAM) interact with their counterparts in a homotypic fashion, and interaction of their intracellular domains with, ZO‐1, cingulin, afadin and α‐catenin complexes links tight junction with cytoskeleton.

Figure 7. Figure 7.

Rho GTPase‐activated cellular mechanisms leading to increased endothelial permeability. Activated Rho inhibits actin depolymerization and stimulates increased stress fiber formation by Rho‐associated kinase (Rho kinase)‐mediated activation of LIM kinase, which in turn phosphorylates and inactivates actin depolymerizing protein cofilin. Rho‐kinase also promotes actomyosin contraction and formation of paracellular gaps in endothelial monolayers via phosphorylation and inactivation of myosin light chain phosphatase (MLCP) leading to accumulation of phosphorylated myosin light chains. Rho induces linear actin polymerization controlled by Rho effector mDia and indirectly, via PIP 5‐kinase mediated effects on regulator of actin polymerization profilin. Rho activation engages PIP 5‐kinase and focal adhesion kinase (FAK), which stimulate interaction between vinculin, talin, FAK, p130Cas, paxillin, and other focal adhesion proteins and promote assembly of focal adhesions critical for anchorage of activated stress fibers and force development by endothelial cells leading to paracellular gap formation and increased endothelial permeability.

Figure 8. Figure 8.

Barrier protective cytoskeletal mechanisms activated by Rac and Cdc42.

Figure 9. Figure 9.

Barrier protective cytoskeletal mechanisms activated by Rap.

Figure 10. Figure 10.

Barrier protective mechanisms mediated by PI3 kinase.

Figure 11. Figure 11.

Barrier protective mechanisms induced by increase in intracellular cAMP.

Figure 12. Figure 12.

Barrier disruptive and barrier protective mechanisms mediated by p60Src tyrosine kinase.

Figure 13. Figure 13.

Barrier protective mechanisms induced by activated protein C.

Figure 14. Figure 14.

Scheme of arachidonic acid metabolic pathway.

Figure 15. Figure 15.

Sphingomyelin metabolic pathway.

Figure 16. Figure 16.

Molecular mechanisms underlying barrier protective effects of sphingosine 1‐phosphate.

Figure 17. Figure 17.

Products of oxidation of phospholipids containing arachidonic acid.

Figure 18. Figure 18.

Barrier protective mechanisms of oxidized phospholipids.

Figure 19. Figure 19.

Barrier protective mechanisms induced by hepatocyte growth factor.

Figure 20. Figure 20.

Barrier protective mechanisms induced by ATP.



Figure 1.

Classification of pulmonary edema.



Figure 2.

Role of Cdc42, Rac, and Rho GTPases in actin cytoskeletal remodeling.



Figure 3.

Regulation of endothelial permeability by microtubule‐dependent signaling. Stable microtubules destabilization by microtubule toxins, bacterial endotoxin, cytokines, or edemagenic agonists (thrombin) causes release of Rho‐specific guanine nucleotide exchange factor GEF‐H1 leading to activation of Rho signaling, actin cytoskeletal remodeling, actomyosin contraction and endothelial permeability. Activation of GEF‐H1 may be inhibited by stabilization of microtubule or activation of Rac and its effector p21‐activated kinase 1 (PAK‐1).



Figure 4.

Schematic representation of focal adhesion protein complex linked via αβ‐integrin heterodimers to the extracellular matrix and via α‐actinin and vinculin linker proteins to the actin cytoskeleton.



Figure 5.

Scheme of adherens junction complex. Cell‐cell contacts are formed by homotypic interactions of transmembrane protein VE‐cadherin, which interacts with αβγ‐catenin complex and p120‐catenin via intracellular domains. Anchorage of adherens junctions to actin cytoskeleton is primarily controlled by α‐catenin and α‐actinin, but may also involve vinculin and ZO proteins. Interaction of Rac/Cdc42 effector IQRas GTPase‐activating protein 1 with either actin cytoskeleton, or beta‐catenin is regulated by Rac/Cdc42 activities and may represent a Rac/Cdc42‐dependent mechanism regulating adherens junction assembly and endothelial barrier.



Figure 6.

Structure of tight junction complex. Extracellular domains of claudin, occluding, or junctional adhesion molecule (JAM) interact with their counterparts in a homotypic fashion, and interaction of their intracellular domains with, ZO‐1, cingulin, afadin and α‐catenin complexes links tight junction with cytoskeleton.



Figure 7.

Rho GTPase‐activated cellular mechanisms leading to increased endothelial permeability. Activated Rho inhibits actin depolymerization and stimulates increased stress fiber formation by Rho‐associated kinase (Rho kinase)‐mediated activation of LIM kinase, which in turn phosphorylates and inactivates actin depolymerizing protein cofilin. Rho‐kinase also promotes actomyosin contraction and formation of paracellular gaps in endothelial monolayers via phosphorylation and inactivation of myosin light chain phosphatase (MLCP) leading to accumulation of phosphorylated myosin light chains. Rho induces linear actin polymerization controlled by Rho effector mDia and indirectly, via PIP 5‐kinase mediated effects on regulator of actin polymerization profilin. Rho activation engages PIP 5‐kinase and focal adhesion kinase (FAK), which stimulate interaction between vinculin, talin, FAK, p130Cas, paxillin, and other focal adhesion proteins and promote assembly of focal adhesions critical for anchorage of activated stress fibers and force development by endothelial cells leading to paracellular gap formation and increased endothelial permeability.



Figure 8.

Barrier protective cytoskeletal mechanisms activated by Rac and Cdc42.



Figure 9.

Barrier protective cytoskeletal mechanisms activated by Rap.



Figure 10.

Barrier protective mechanisms mediated by PI3 kinase.



Figure 11.

Barrier protective mechanisms induced by increase in intracellular cAMP.



Figure 12.

Barrier disruptive and barrier protective mechanisms mediated by p60Src tyrosine kinase.



Figure 13.

Barrier protective mechanisms induced by activated protein C.



Figure 14.

Scheme of arachidonic acid metabolic pathway.



Figure 15.

Sphingomyelin metabolic pathway.



Figure 16.

Molecular mechanisms underlying barrier protective effects of sphingosine 1‐phosphate.



Figure 17.

Products of oxidation of phospholipids containing arachidonic acid.



Figure 18.

Barrier protective mechanisms of oxidized phospholipids.



Figure 19.

Barrier protective mechanisms induced by hepatocyte growth factor.



Figure 20.

Barrier protective mechanisms induced by ATP.

References
 1. Aaronson SA, Bottaro DP, Miki T, Ron D, Finch PW, Fleming TP, Ahn J, Taylor WG, Rubin JS. Keratinocyte growth factor. A fibroblast growth factor family member with unusual target cell specificity. Ann N Y Acad Sci 638: 62‐77, 1991.
 2. Abe K, Rossman KL, Liu B, Ritola KD, Chiang D, Campbell SL, Burridge K, Der CJ. Vav2 is an activator of Cdc42, Rac1, and RhoA. J Biol Chem 275: 10141‐10149, 2000.
 3. Aberle H, Schwartz H, Kemler R. Cadherin‐catenin complex: Protein interactions and their implications for cadherin function. J Cell Biochem 61: 514‐523, 1996.
 4. Abraham E, Laterre PF, Garg R, Levy H, Talwar D, Trzaskoma BL, Francois B, Guy JS, Bruckmann M, Rea‐Neto A, Rossaint R, Perrotin D, Sablotzki A, Arkins N, Utterback BG, Macias WL. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med 353: 1332‐1341, 2005.
 5. Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL, Beale R, Svoboda P, Laterre PF, Simon S, Light B, Spapen H, Stone J, Seibert A, Peckelsen C, De Deyne C, Postier R, Pettila V, Artigas A, Percell SR, Shu V, Zwingelstein C, Tobias J, Poole L, Stolzenbach JC, Creasey AA. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: A randomized controlled trial. JAMA 290: 238‐247, 2003.
 6. Adams JM, Hauser CJ, Livingston DH, Lavery RF, Fekete Z, Deitch EA. Early trauma polymorphonuclear neutrophil responses to chemokines are associated with development of sepsis, pneumonia, and organ failure. J Trauma 51: 452‐456; discussion 456‐457, 2001.
 7. Adamson RH, Zeng M, Adamson GN, Lenz JF, Curry FE. PAF‐ and bradykinin‐induced hyperpermeability of rat venules is independent of actin‐myosin contraction. Am J Physiol Heart Circ Physiol 285: H406‐H417, 2003.
 8. Aghazadeh B, Lowry WE, Huang XY, Rosen MK. Structural basis for relief of autoinhibition of the Dbl homology domain of proto‐oncogene Vav by tyrosine phosphorylation. Cell 102: 625‐633, 2000.
 9. Ahluwalia A, MacAllister RJ, Hobbs AJ. Vascular actions of natriuretic peptides. Cyclic GMP‐dependent and ‐independent mechanisms. Basic Res Cardiol 99: 83‐89, 2004.
 10. Alfranca A, Iniguez MA, Fresno M, Redondo JM. Prostanoid signal transduction and gene expression in the endothelium: Role in cardiovascular diseases. Cardiovasc Res 70: 446‐456, 2006.
 11. Ali MH, Mungai PT, Schumacker PT. Stretch‐induced phosphorylation of focal adhesion kinase in endothelial cells: Role of mitochondrial oxidants. Am J Physiol 291: L38‐L45, 2006.
 12. Allport JR, Muller WA, Luscinskas FW. Monocytes induce reversible focal changes in vascular endothelial cadherin complex during transendothelial migration under flow. J Cell Biol 148: 203‐216, 2000.
 13. Anand‐Srivastava MB. Natriuretic peptide receptor‐C signaling and regulation. Peptides 26: 1044‐1059, 2005.
 14. Andonegui G, Goyert SM, Kubes P. Lipopolysaccharide‐induced leukocyte‐endothelial cell interactions: A role for CD14 versus toll‐like receptor 4 within microvessels. J Immunol 169: 2111‐2119, 2002.
 15. Antonov A, Snead C, Gorshkov B, Antonova GN, Verin AD, Catravas JD. Heat shock protein 90 inhibitors protect and restore pulmonary endothelial barrier function. Am J Respir Cell Mol Biol 39: 551‐559, 2008.
 16. Aoki M, Morishita R, Taniyama Y, Kaneda Y, Ogihara T. Therapeutic angiogenesis induced by hepatocyte growth factor: Potential gene therapy for ischemic diseases. J Atheroscler Thromb 7: 71‐76, 2000.
 17. Arber S, Barbayannis FA, Hanser H, Schneider C, Stanyon CA, Bernard O, Caroni P. Regulation of actin dynamics through phosphorylation of cofilin by LIM‐kinase. Nature 393: 805‐809, 1998.
 18. Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, Frees K, Watt JL, Schwartz DA. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 25: 187‐191, 2000.
 19. Arthur WT, Quilliam LA, Cooper JA. Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors. J Cell Biol 167: 111‐122, 2004.
 20. Atabai K, Ishigaki M, Geiser T, Ueki I, Matthay MA, Ware LB. Keratinocyte growth factor can enhance alveolar epithelial repair by nonmitogenic mechanisms. Am J Physiol 283: L163‐L169, 2002.
 21. Aurrand‐Lions M, Johnson‐Leger C, Wong C, Du Pasquier L, Imhof BA. Heterogeneity of endothelial junctions is reflected by differential expression and specific subcellular localization of the three JAM family members. Blood 98: 3699‐3707, 2001.
 22. Ayalon O, Sabanai H, Lampugnani MG, Dejana E, Geiger B. Spatial and temporal relationships between cadherins and PECAM‐1 in cell‐cell junctions of human endothelial cells. J Cell Biol 126: 247‐258, 1994.
 23. Baba Y, Yazawa T, Kanegae Y, Sakamoto S, Saito I, Morimura N, Goto T, Yamada Y, Kurahashi K. Keratinocyte growth factor gene transduction ameliorates acute lung injury and mortality in mice. Hum Gene Ther 18: 130‐141, 2007.
 24. Backer JM, Myers MG, Jr, Shoelson SE, Chin DJ, Sun XJ, Miralpeix M, Hu P, Margolis B, Skolnik EY, Schlessinger J. Phosphatidylinositol 3′‐kinase is activated by association with IRS‐1 during insulin stimulation. EMBO J 11: 3469‐3479, 1992.
 25. Bae JS, Rezaie AR. Protease activated receptor 1 (PAR‐1) activation by thrombin is protective in human pulmonary artery endothelial cells if endothelial protein C receptor is occupied by its natural ligand. Thromb Haemost 100: 101‐109, 2008.
 26. Bae JS, Yang L, Manithody C, Rezaie AR. The ligand occupancy of endothelial protein C receptor switches the protease‐activated receptor 1‐dependent signaling specificity of thrombin from a permeability‐enhancing to a barrier‐protective response in endothelial cells. Blood 110: 3909‐3916, 2007.
 27. Bae JS, Yang L, Rezaie AR. Receptors of the protein C activation and activated protein C signaling pathways are colocalized in lipid rafts of endothelial cells. Proc Natl Acad Sci U S A 104: 2867‐2872, 2007.
 28. Bagrodia S, Cerione RA. Pak to the future. Trends Cell Biol 9: 350‐355, 1999.
 29. Bailey TC, Da Silva KA, Lewis JF, Rodriguez‐Capote K, Possmayer F, Veldhuizen RA. Physiological and inflammatory response to instillation of an oxidized surfactant in a rat model of surfactant deficiency. J Appl Physiol 96: 1674‐1680, 2004.
 30. Bailey TC, Martin EL, Zhao L, Veldhuizen RA. High oxygen concentrations predispose mouse lungs to the deleterious effects of high stretch ventilation. J Appl Physiol 94: 975‐982, 2003.
 31. Balda MS, Gonzalez‐Mariscal L, Matter K, Cereijido M, Anderson JM. Assembly of the tight junction: The role of diacylglycerol. J Cell Biol 123: 293‐302, 1993.
 32. Bamforth SD, Kniesel U, Wolburg H, Engelhardt B, Risau W. A dominant mutant of occludin disrupts tight junction structure and function. J Cell Sci 112(Pt 12): 1879‐1888, 1999.
 33. Bao S, Wang Y, Sweeney P, Chaudhuri A, Doseff AI, Marsh CB, Knoell DL. Keratinocyte growth factor induces Akt kinase activity and inhibits Fas‐mediated apoptosis in A549 lung epithelial cells. Am J Physiol 288: L36‐L42, 2005.
 34. Barazzone C, Donati YR, Rochat AF, Vesin C, Kan CD, Pache JC, Piguet PF. Keratinocyte growth factor protects alveolar epithelium and endothelium from oxygen‐induced injury in mice. Am J Pathol 154: 1479‐1487, 1999.
 35. Bazzoni G. Endothelial tight junctions: Permeable barriers of the vessel wall. Thromb Haemost 95: 36‐42, 2006.
 36. Bazzoni G, Dejana E. Endothelial cell‐to‐cell junctions: Molecular organization and role in vascular homeostasis. Physiol Rev 84: 869‐901, 2004.
 37. Bazzoni G, Martinez‐Estrada OM, Orsenigo F, Cordenonsi M, Citi S, Dejana E. Interaction of junctional adhesion molecule with the tight junction components ZO‐1, cingulin, and occludin. J Biol Chem 275: 20520‐20526, 2000.
 38. Bear JE, Rawls JF, Saxe CL, III. SCAR, a WASP‐related protein, isolated as a suppressor of receptor defects in late Dictyostelium development. J Cell Biol 142: 1325‐1335, 1998.
 39. Beckers CM, van Hinsbergh VW, van Nieuw Amerongen GP. Driving Rho GTPase activity in endothelial cells regulates barrier integrity. Thromb Haemost 103: 40‐55, 2010.
 40. Behzadian MA, Wang XL, Windsor LJ, Ghaly N, Caldwell RB. TGF‐beta increases retinal endothelial cell permeability by increasing MMP‐9: Possible role of glial cells in endothelial barrier function. Invest Ophthalmol Vis Sci 42: 853‐859, 2001.
 41. Benz PM, Blume C, Moebius J, Oschatz C, Schuh K, Sickmann A, Walter U, Feller SM, Renne T. Cytoskeleton assembly at endothelial cell‐cell contacts is regulated by alphaII‐spectrin‐VASP complexes. J Cell Biol 180: 205‐219, 2008.
 42. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez‐Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ, Jr. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344: 699‐709, 2001.
 43. Bershadsky AD, Balaban NQ, Geiger B. Adhesion‐dependent cell mechanosensitivity. Annu Rev Cell Dev Biol 19: 677‐695, 2003.
 44. Bershadsky AD, Ballestrem C, Carramusa L, Zilberman Y, Gilquin B, Khochbin S, Alexandrova AY, Verkhovsky AB, Shemesh T, Kozlov MM. Assembly and mechanosensory function of focal adhesions: Experiments and models. Eur J Cell Biol 85: 165‐173, 2006.
 45. Bertuglia S, Veronese FM, Pasut G. Polyethylene glycol and a novel developed polyethylene glycol‐nitric oxide normalize arteriolar response and oxidative stress in ischemia‐reperfusion. Am J Physiol Heart Circ Physiol 291: H1536‐H1544, 2006.
 46. Birkenfeld J, Nalbant P, Yoon SH, Bokoch GM. Cellular functions of GEF‐H1, a microtubule‐regulated Rho‐GEF: Is altered GEF‐H1 activity a crucial determinant of disease pathogenesis? Trends Cell Biol 18: 210‐219, 2008.
 47. Birukov KG, Birukova AA, Dudek SM, Verin AD, Crow MT, Zhan X, DePaola N, Garcia JG. Shear stress‐mediated cytoskeletal remodeling and cortactin translocation in pulmonary endothelial cells. Am J Respir Cell Mol Biol 26: 453‐464, 2002.
 48. Birukov KG, Bochkov VN, Birukova AA, Kawkitinarong K, Rios A, Leitner A, Verin AD, Bokoch GM, Leitinger N, Garcia JG. Epoxycyclopentenone‐containing oxidized phospholipids restore endothelial barrier function via Cdc42 and Rac. Circ Res 95: 892‐901, 2004.
 49. Birukov KG, Csortos C, Marzilli L, Dudek S, Ma SF, Bresnick AR, Verin AD, Cotter RJ, Garcia JG. Differential regulation of alternatively spliced endothelial cell myosin light chain kinase isoforms by p60(Src). J Biol Chem 276: 8567‐8573, 2001.
 50. Birukov KG, Jacobson JR, Flores AA, Ye SQ, Birukova AA, Verin AD, Garcia JG. Magnitude‐dependent regulation of pulmonary endothelial cell barrier function by cyclic stretch. Am J Physiol 285: L785‐L797, 2003.
 51. Birukov KG, Leitinger N, Bochkov VN, Garcia JG. Signal transduction pathways activated in human pulmonary endothelial cells by OxPAPC, a bioactive component of oxidized lipoproteins. Microvasc Res 67: 18‐28, 2004.
 52. Birukova AA, Adyshev D, Gorshkov B, Birukov KG, Verin AD. ALK5 and Smad4 are involved in TGF‐beta1‐induced pulmonary endothelial permeability. FEBS Lett 579: 4031‐4037, 2005.
 53. Birukova AA, Adyshev D, Gorshkov B, Bokoch GM, Birukov KG, Verin AA. GEF‐H1 is involved in agonist‐induced human pulmonary endothelial barrier dysfunction. Am J Physiol 290: L540‐L548, 2006.
 54. Birukova AA, Alekseeva E, Cokic I, Turner CE, Birukov KG. Cross talk between paxillin and Rac is critical for mediation of barrier‐protective effects by oxidized phospholipids. Am J Physiol 295: L593‐L602, 2008.
 55. Birukova AA, Alekseeva E, Mikaelyan A, Birukov KG. HGF attenuates thrombin‐induced permeability in the human pulmonary endothelial cells by Tiam1‐mediated activation of the Rac pathway and by Tiam1/Rac‐dependent inhibition of the Rho pathway. Faseb J 21: 2776‐2786, 2007.
 56. Birukova AA, Arce FT, Moldobaeva N, Dudek SM, Garcia JG, Lal R, Birukov KG. Endothelial permeability is controlled by spatially defined cytoskeletal mechanics: Atomic force microscopy force mapping of pulmonary endothelial monolayer. Nanomedicine 5: 30‐41, 2009.
 57. Birukova AA, Birukov KG, Adyshev D, Usatyuk P, Natarajan V, Garcia JG, Verin AD. Involvement of microtubules and Rho pathway in TGF‐beta1‐induced lung vascular barrier dysfunction. J Cell Physiol 204: 934‐947, 2005.
 58. Birukova AA, Birukov KG, Smurova K, Adyshev DM, Kaibuchi K, Alieva I, Garcia JG, Verin AD. Novel role of microtubules in thrombin‐induced endothelial barrier dysfunction. Faseb J 18: 1879‐1890, 2004.
 59. Birukova AA, Burdette D, Moldobaeva N, Xing J, Fu P, Birukov KG. Rac GTPase is a hub for protein kinase A and Epac signaling in endothelial barrier protection by cAMP. Microvasc Res 79: 128‐138, 2010.
 60. Birukova AA, Chatchavalvanich S, Oskolkova O, Bochkov VN, Birukov KG. Signaling pathways involved in OxPAPC‐induced pulmonary endothelial barrier protection. Microvasc Res 73: 173‐181, 2007.
 61. Birukova AA, Chatchavalvanich S, Rios A, Kawkitinarong K, Garcia JG, Birukov KG. Differential regulation of pulmonary endothelial monolayer integrity by varying degrees of cyclic stretch. Am J Pathol 168: 1749‐1761, 2006.
 62. Birukova AA, Cokic I, Moldobaeva N, Birukov KG. Paxillin is involved in the differential regulation of endothelial barrier by HGF and VEGF. Am J Respir Cell Mol Biol 40: 99‐107, 2008.
 63. Birukova AA, Fu P, Chatchavalvanich S, Burdette D, Oskolkova O, Bochkov VN, Birukov KG. Polar head groups are important for barrier protective effects of oxidized phospholipids on pulmonary endothelium. Am J Physiol 292: L924‐L935, 2007.
 64. Birukova AA, Fu P, Xing J, Birukov KG. Rap1 mediates protective effects of iloprost against ventilator induced lung injury. J Appl Physiol 107: 1900‐1910, 2009.
 65. Birukova AA, Fu P, Xing J, Cokic I, Birukov KG. Lung endothelial barrier protection by iloprost in the 2‐hit models of ventilator‐induced lung injury (VILI) involves inhibition of Rho signaling. Transl Res 155: 44‐54, 2010.
 66. Birukova AA, Fu P, Xing J, Yakubov B, Cokic I, Birukov KG. Mechanotransduction by GEF‐H1 as a novel mechanism of ventilator‐induced vascular endothelial permeability. Am J Physiol 298: L837‐L848, 2010.
 67. Birukova AA, Liu F, Garcia JG, Verin AD. Protein kinase A attenuates endothelial cell barrier dysfunction induced by microtubule disassembly. Am J Physiol 287: L86‐L93, 2004.
 68. Birukova AA, Malyukova I, Mikaelyan A, Fu P, Birukov KG. Tiam1 and betaPIX mediate Rac‐dependent endothelial barrier protective response to oxidized phospholipids. J Cell Physiol 211: 608‐617, 2007.
 69. Birukova AA, Malyukova I, Poroyko V, Birukov KG. Paxillin ‐ {beta}‐catenin interactions are involved in Rac/Cdc42‐mediated endothelial barrier‐protective response to oxidized phospholipids. Am J Physiol 293: L199‐L211, 2007.
 70. Birukova AA, Moldobaeva N, Xing J, Birukov KG. Magnitude‐dependent effects of cyclic stretch on HGF‐ and VEGF‐induced pulmonary endothelial remodeling and barrier regulation. Am J Physiol 295: L612‐L623, 2008.
 71. Birukova AA, Rios A, Birukov KG. Long‐term cyclic stretch controls pulmonary endothelial permeability at translational and post‐translational levels. Exp Cell Res 314: 3466‐3477, 2008.
 72. Birukova AA, Smurova K, Birukov KG, Kaibuchi K, Garcia JGN, Verin AD. Role of Rho GTPases in thrombin‐induced lung vascular endothelial cells barrier dysfunction. Microvasc Res 67: 64‐77, 2004.
 73. Birukova AA, Smurova K, Birukov KG, Usatyuk P, Liu F, Kaibuchi K, Ricks‐Cord A, Natarajan V, Alieva I, Garcia JG, Verin AD. Microtubule disassembly induces cytoskeletal remodeling and lung vascular barrier dysfunction: Role of Rho‐dependent mechanisms. J Cell Physiol 201: 55‐70, 2004.
 74. Birukova AA, Xing J, Fu P, Yakubov B, Dubrovskyi O, Fortune JA, Klibanov AM, Birukov KG. Atrial natriuretic peptide attenuates LPS‐induced lung vascular leak: Role of PAK1. Am J Physiol 299: L652‐L663, 2010.
 75. Birukova AA, Zagranichnaya T, Alekseeva E, Bokoch GM, Birukov KG. Epac/Rap and PKA are novel mechanisms of ANP‐induced Rac‐mediated pulmonary endothelial barrier protection. J Cell Physiol 215: 715‐724, 2008.
 76. Birukova AA, Zagranichnaya T, Alekseeva E, Fu P, Chen W, Jacobson JR, Birukov KG. Prostaglandins PGE2 and PGI2 promote endothelial barrier enhancement via PKA‐ and Epac1/Rap1‐dependent Rac activation. Exp Cell Res 313: 2504‐2520, 2007.
 77. Bishop AL, Hall A. Rho GTPases and their effector proteins. Biochem J 348(Pt 2): 241‐255, 2000.
 78. Blagg BS, Kerr TD. Hsp90 inhibitors: Small molecules that transform the Hsp90 protein folding machinery into a catalyst for protein degradation. Med Res Rev 26: 310‐338, 2006.
 79. Bochkov VN, Leitinger N. Anti‐inflammatory properties of lipid oxidation products. J Mol Med 81: 613‐626, 2003.
 80. Bochkov VN, Leitinger N, Birukov KG. Role of oxidized phospholipids in acute lung injury. Curr Resp Med Rev 2: 27‐37, 2006.
 81. Bochkov VN, Oskolkova OV, Birukov KG, Levonen AL, Binder CJ, Stockl J. Generation and biological activities of oxidized phospholipids. Antioxid Redox Signal 12: 1009‐1059, 2010.
 82. Bodin P, Burnstock G. ATP‐stimulated release of ATP by human endothelial cells. J Cardiovasc Pharmacol 27: 872‐875, 1996.
 83. Bodin P, Burnstock G. Increased release of ATP from endothelial cells during acute inflammation. Inflamm Res 47: 351‐354, 1998.
 84. Bogatcheva NV, Verin AD. The role of cytoskeleton in the regulation of vascular endothelial barrier function. Microvasc Res 76: 202‐207, 2008.
 85. Boguski MS, McCormick F. Proteins regulating Ras and its relatives. Nature 366: 643‐654, 1993.
 86. Bokoch GM. Biology of the p21‐Activated Kinases. Annu Rev Biochem 72: 743‐781, 2003.
 87. Borgens RB, Shi R. Immediate recovery from spinal cord injury through molecular repair of nerve membranes with polyethylene glycol. Faseb J 14: 27‐35, 2000.
 88. Borisy GG, Svitkina TM. Actin machinery: Pushing the envelope. Curr Opin Cell Biol 12: 104‐112, 2000.
 89. Bos CL, Richel DJ, Ritsema T, Peppelenbosch MP, Versteeg HH. Prostanoids and prostanoid receptors in signal transduction. Int J Biochem Cell Biol 36: 1187‐1205, 2004.
 90. Bos JL. Epac: A new cAMP target and new avenues in cAMP research. Nat Rev Mol Cell Biol 4: 733‐738, 2003.
 91. Bos JL. Linking Rap to cell adhesion. Curr Opin Cell Biol 17: 123‐128, 2005.
 92. Bos JL. Epac proteins: Multi‐purpose cAMP targets. Trends Biochem Sci 2006.
 93. Bos JL, de Rooij J, Reedquist KA. Rap1 signalling: Adhering to new models. Nat Rev Mol Cell Biol 2: 369‐377, 2001.
 94. Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA. Identification of the hepatocyte growth factor receptor as the c‐met proto‐oncogene product. Science 251: 802‐804, 1991.
 95. Braga VM, Del Maschio A, Machesky L, Dejana E. Regulation of cadherin function by Rho and Rac: Modulation by junction maturation and cellular context. Mol Biol Cell 10: 9‐22, 1999.
 96. Breyer RM, Bagdassarian CK, Myers SA, Breyer MD. Prostanoid receptors: Subtypes and signaling. Annu Rev Pharmacol Toxicol 41: 661‐690, 2001.
 97. Briggs MW, Sacks DB. IQGAP proteins are integral components of cytoskeletal regulation. EMBO Rep 4: 571‐574, 2003.
 98. Brindle NP, Saharinen P, Alitalo K. Signaling and functions of angiopoietin‐1 in vascular protection. Circ Res 98: 1014‐1023, 2006.
 99. Brinkmann V, Cyster JG, Hla T. FTY720: Sphingosine 1‐phosphate receptor‐1 in the control of lymphocyte egress and endothelial barrier function. Am J Transplant 4: 1019‐1025, 2004.
 100. Broemer M, Krappmann D, Scheidereit C. Requirement of Hsp90 activity for IkappaB kinase (IKK) biosynthesis and for constitutive and inducible IKK and NF‐kappaB activation. Oncogene 23: 5378‐5386, 2004.
 101. Broman MT, Kouklis P, Gao X, Ramchandran R, Neamu RF, Minshall RD, Malik AB. Cdc42 regulates adherens junction stability and endothelial permeability by inducing alpha‐catenin interaction with the vascular endothelial cadherin complex. Circ Res 98: 73‐80, 2006.
 102. Broman MT, Mehta D, Malik AB. Cdc42 regulates the restoration of endothelial adherens junctions and permeability. Trends Cardiovasc Med 17: 151‐156, 2007.
 103. Brown MC, Turner CE. Paxillin: Adapting to change. Physiol Rev 84: 1315‐1339, 2004.
 104. Brown MC, West KA, Turner CE. Paxillin‐dependent paxillin kinase linker and p21‐activated kinase localization to focal adhesions involves a multistep activation pathway. Mol Biol Cell 13: 1550‐1565, 2002.
 105. Bussolino F, Serini G, Mitola S, Bazzoni G, Dejana E. Dynamic modules and heterogeneity of function: A lesson from tyrosine kinase receptors in endothelial cells. EMBO Rep 2: 763‐767, 2001.
 106. Bustelo XR. Regulatory and signaling properties of the Vav family. Mol Cell Biol 20: 1461‐1477, 2000.
 107. Calfee CS, Matthay MA. Nonventilatory treatments for acute lung injury and ARDS. Chest 131: 913‐920, 2007.
 108. Callow MG, Zozulya S, Gishizky ML, Jallal B, Smeal T. PAK4 mediates morphological changes through the regulation of GEF‐H1. J Cell Sci 118: 1861‐1872, 2005.
 109. Cantor JO, Turino GM. Can exogenously administered hyaluronan improve respiratory function in patients with pulmonary emphysema? Chest 125: 288‐292, 2004.
 110. Carbajal JM, Schaeffer RC, Jr. RhoA inactivation enhances endothelial barrier function. Am J Physiol 277: C955‐C964, 1999.
 111. Carlier MF. Control of actin dynamics. Curr Opin Cell Biol 10: 45‐51, 1998.
 112. Carlson TR, Feng Y, Maisonpierre PC, Mrksich M, Morla AO. Direct cell adhesion to the angiopoietins mediated by integrins. J Biol Chem 276: 26516‐26525, 2001.
 113. Carmeliet P, Lampugnani MG, Moons L, Breviario F, Compernolle V, Bono F, Balconi G, Spagnuolo R, Oosthuyse B, Dewerchin M, Zanetti A, Angellilo A, Mattot V, Nuyens D, Lutgens E, Clotman F, de Ruiter MC, Gittenberger‐de Groot A, Poelmann R, Lupu F, Herbert JM, Collen D, Dejana E. Targeted deficiency or cytosolic truncation of the VE‐cadherin gene in mice impairs VEGF‐mediated endothelial survival and angiogenesis. Cell 98: 147‐157, 1999.
 114. Carpenter CL, Auger KR, Chanudhuri M, Yoakim M, Schaffhausen B, Shoelson S, Cantley LC. Phosphoinositide 3‐kinase is activated by phosphopeptides that bind to the SH2 domains of the 85‐kDa subunit. J Biol Chem 268: 9478‐9483, 1993.
 115. Carpenter CT, Price PV, Christman BW. Exhaled breath condensate isoprostanes are elevated in patients with acute lung injury or ARDS. Chest 114: 1653‐1659, 1998.
 116. Cevallos M, Riha GM, Wang X, Yang H, Yan S, Li M, Chai H, Yao Q, Chen C. Cyclic strain induces expression of specific smooth muscle cell markers in human endothelial cells. Differentiation 74: 552‐561, 2006.
 117. Chabot F, Mitchell JA, Gutteridge JM, Evans TW. Reactive oxygen species in acute lung injury. Eur Respir J 11: 745‐757, 1998.
 118. Chadli A, Bouhouche I, Sullivan W, Stensgard B, McMahon N, Catelli MG, Toft DO. Dimerization and N‐terminal domain proximity underlie the function of the molecular chaperone heat shock protein 90. Proc Natl Acad Sci U S A 97: 12524‐12529, 2000.
 119. Chakraborti S, Gurtner GH, Michael JR. Oxidant‐mediated activation of phospholipase A2 in pulmonary endothelium. Am J Physiol 257: L430‐L437, 1989.
 120. Chatterjee A, Dimitropoulou C, Drakopanayiotakis F, Antonova G, Snead C, Cannon J, Venema RC, Catravas JD. Heat shock protein 90 inhibitors prolong survival, attenuate inflammation, and reduce lung injury in murine sepsis. Am J Respir Crit Care Med 176: 667‐675, 2007.
 121. Chatterjee A, Snead C, Yetik‐Anacak G, Antonova G, Zeng J, Catravas JD. Heat shock protein 90 inhibitors attenuate LPS‐induced endothelial hyperpermeability. Am J Physiol 294: L755‐L763, 2008.
 122. Chen H, Bernstein BW, Bamburg JR. Regulating actin‐filament dynamics in vivo. Trends Biochem Sci 25: 19‐23, 2000.
 123. Chen KD, Li YS, Kim M, Li S, Yuan S, Chien S, Shyy JY. Mechanotransduction in response to shear stress. Roles of receptor tyrosine kinases, integrins, and Shc. J Biol Chem 274: 18393‐18400, 1999.
 124. Chen W, Pendyala S, Natarajan V, Garcia JG, Jacobson JR. Endothelial cell barrier protection by simvastatin: GTPase regulation and NADPH oxidase inhibition. Am J Physiol 295: L575‐L583, 2008.
 125. Chen Y, Wang Y, Yu H, Wang F, Xu W. The cross talk between protein kinase A‐ and RhoA‐mediated signaling in cancer cells. Exp Biol Med (Maywood) 230: 731‐741, 2005.
 126. Cheng T, Liu D, Griffin JH, Fernandez JA, Castellino F, Rosen ED, Fukudome K, Zlokovic BV. Activated protein C blocks p53‐mediated apoptosis in ischemic human brain endothelium and is neuroprotective. Nat Med 9: 338‐342, 2003.
 127. Chiang ET, Camp SM, Dudek SM, Brown ME, Usatyuk PV, Zaborina O, Alverdy JC, Garcia JG. Protective effects of high‐molecular weight polyethylene glycol (PEG) in human lung endothelial cell barrier regulation: Role of actin cytoskeletal rearrangement. Microvasc Res 77: 174‐186, 2009.
 128. Christensen AE, Selheim F, de Rooij J, Dremier S, Schwede F, Dao KK, Martinez A, Maenhaut C, Bos JL, Genieser HG, Doskeland SO. cAMP analog mapping of Epac1 and cAMP kinase. Discriminating analogs demonstrate that Epac and cAMP kinase act synergistically to promote PC‐12 cell neurite extension. J Biol Chem 278: 35394‐35402, 2003.
 129. Civelekoglu‐Scholey G, Orr AW, Novak I, Meister JJ, Schwartz MA, Mogilner A. Model of coupled transient changes of Rac, Rho, adhesions and stress fibers alignment in endothelial cells responding to shear stress. J Theor Biol 232: 569‐585, 2005.
 130. Comerford KM, Lawrence DW, Synnestvedt K, Levi BP, Colgan SP. Role of vasodilator‐stimulated phosphoprotein in PKA‐induced changes in endothelial junctional permeability. Faseb J 16: 583‐585, 2002.
 131. Corada M, Zanetta L, Orsenigo F, Breviario F, Lampugnani MG, Bernasconi S, Liao F, Hicklin DJ, Bohlen P, Dejana E. A monoclonal antibody to vascular endothelial‐cadherin inhibits tumor angiogenesis without side effects on endothelial permeability. Blood 100: 905‐911, 2002.
 132. Coughlin SR. Thrombin signalling and protease‐activated receptors. Nature 407: 258‐264, 2000.
 133. Creasey AA, Chang AC, Feigen L, Wun TC, Taylor FB, Jr, Hinshaw LB. Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. J Clin Invest 91: 2850‐2860, 1993.
 134. Critchley DR. Focal adhesions ‐ the cytoskeletal connection. Curr Opin Cell Biol 12: 133‐139, 2000.
 135. Crosby LM, Waters CM. Epithelial repair mechanisms in the lung. Am J Physiol 298: L715‐L731, 2010.
 136. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. Inhibition of glycogen synthase kinase‐3 by insulin mediated by protein kinase B. Nature 378: 785‐789, 1995.
 137. Cui L, Chen C, Xu T, Zhang J, Shang X, Luo J, Chen L, Ba X, Zeng X. c‐Abl kinase is required for beta 2 integrin‐mediated neutrophil adhesion. J Immunol 182: 3233‐3242, 2009.
 138. Cullere X, Shaw SK, Andersson L, Hirahashi J, Luscinskas FW, Mayadas TN. Regulation of vascular endothelial barrier function by Epac, a cAMP‐activated exchange factor for Rap GTPase. Blood 105: 1950‐1955, 2005.
 139. Curtis TM, McKeown‐Longo PJ, Vincent PA, Homan SM, Wheatley EM, Saba TM. Fibronectin attenuates increased endothelial monolayer permeability after RGD peptide, anti‐alpha 5 beta 1, or TNF‐alpha exposure. Am J Physiol 269: L248‐L260, 1995.
 140. Date I, Takagi N, Takagi K, Kago T, Matsumoto K, Nakamura T, Takeo S. Hepatocyte growth factor attenuates cerebral ischemia‐induced learning dysfunction. Biochem Biophys Res Commun 319: 1152‐1158, 2004.
 141. de Rooij J, Zwartkruis FJ, Verheijen MH, Cool RH, Nijman SM, Wittinghofer A, Bos JL. Epac is a Rap1 guanine‐nucleotide‐exchange factor directly activated by cyclic AMP. Nature 396: 474‐477, 1998.
 142. Defouw LM, Defouw DO. Cyclic GMP‐mediated macromolecular extravasation from angiogenic microvessels in vivo. Endothelium 7: 193‐200, 2000.
 143. DeFouw LM, DeFouw DO. Differential phosphodiesterase activity contributes to restrictive endothelial barrier function during angiogenesis. Microvasc Res 62: 263‐270, 2001.
 144. Deible CR, Beckman EJ, Russell AJ, Wagner WR. Creating molecular barriers to acute platelet deposition on damaged arteries with reactive polyethylene glycol. J Biomed Mater Res 41: 251‐256, 1998.
 145. Dejana E. Endothelial adherens junctions: Implications in the control of vascular permeability and angiogenesis. J Clin Invest 100: S7‐S10, 1997.
 146. Dejana E. Endothelial cell‐cell junctions: Happy together. Nat Rev Mol Cell Biol 5: 261‐270, 2004.
 147. Dejana E, Colella S, Conforti G, Abbadini M, Gaboli M, Marchisio PC. Fibronectin and vitronectin regulate the organization of their respective Arg‐Gly‐Asp adhesion receptors in cultured human endothelial cells. J Cell Biol 107: 1215‐1223, 1988.
 148. Dell'Omo G, Bandinelli S, Penno G, Pedrinelli R, Mariani M. Simvastatin, capillary permeability, and acetylcholine‐mediated vasomotion in atherosclerotic, hypercholesterolemic men. Clin Pharmacol Ther 68: 427‐434, 2000.
 149. DeMaio L, Rouhanizadeh M, Reddy S, Sevanian A, Hwang J, Hsiai TK. Oxidized phospholipids mediate occludin expression and phosphorylation in vascular endothelial cells. Am J Physiol Heart Circ Physiol 290: H674‐H683, 2006.
 150. Desai A, Mitchison TJ. Microtubule polymerization dynamics. Annu Rev Cell Dev Biol 13: 83‐117, 1997.
 151. Desai LP, Sinclair SE, Chapman KE, Hassid A, Waters CM. High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion. Am J Physiol 293: L769‐L778, 2007.
 152. Dodd‐o JM, Hristopoulos ML, Kibler K, Gutkowska J, Mukaddam‐Daher S, Gonzalez A, Welsh‐Servinsky LE, Pearse DB. The role of natriuretic peptide receptor‐A signaling in unilateral lung ischemia‐reperfusion injury in the intact mouse. Am J Physiol 294: L714‐L723, 2008.
 153. Dong JM, Leung T, Manser E, Lim L. cAMP‐induced morphological changes are counteracted by the activated RhoA small GTPase and the Rho kinase ROKalpha. J Biol Chem 273: 22554‐22562, 1998.
 154. Doust JA, Pietrzak E, Dobson A, Glasziou P. How well does B‐type natriuretic peptide predict death and cardiac events in patients with heart failure: Systematic review. Bmj 330: 625, 2005.
 155. Draijer R, Atsma DE, van der Laarse A, van Hinsbergh VW. cGMP and nitric oxide modulate thrombin‐induced endothelial permeability. Regulation via different pathways in human aortic and umbilical vein endothelial cells. Circ Res 76: 199‐208, 1995.
 156. Dubniks M, Grande PO. The effects of activated protein C and prostacyclin on arterial oxygenation and protein leakage in the lung and the gut under endotoxaemia in the rat. Acta Anaesthesiol Scand 52: 381‐387, 2008.
 157. Dudek SM, Birukov KG, Zhan X, Garcia JG. Novel interaction of cortactin with endothelial cell myosin light chain kinase. Biochem Biophys Res Commun 298: 511‐519, 2002.
 158. Dudek SM, Camp SM, Chiang ET, Singleton PA, Usatyuk PV, Zhao Y, Natarajan V, Garcia JG. Pulmonary endothelial cell barrier enhancement by FTY720 does not require the S1P1 receptor. Cell Signal 19: 1754‐1764, 2007.
 159. Dudek SM, Garcia JG. Cytoskeletal regulation of pulmonary vascular permeability. J Appl Physiol 91: 1487‐1500, 2001.
 160. Dudek SM, Jacobson JR, Chiang ET, Birukov KG, Wang P, Zhan X, Garcia JG. Pulmonary endothelial cell barrier enhancement by sphingosine 1‐phosphate: Roles for cortactin and myosin light chain kinase. J Biol Chem 279: 24692‐24700, 2004.
 161. Eison HB, Rosen MJ, Phillips RA, Krakoff LR. Determinants of atrial natriuretic factor in the adult respiratory distress syndrome. Chest 94: 1040‐1045, 1988.
 162. Enomoto T. Microtubule disruption induces the formation of actin stress fibers and focal adhesions in cultured cells: Possible involvement of the rho signal cascade. Cell Struct Funct 21: 317‐326, 1996.
 163. Esser S, Lampugnani MG, Corada M, Dejana E, Risau W. Vascular endothelial growth factor induces VE‐cadherin tyrosine phosphorylation in endothelial cells. J Cell Sci 111(Pt 13): 1853‐1865, 1998.
 164. Essler M, Staddon JM, Weber PC, Aepfelbacher M. Cyclic AMP blocks bacterial lipopolysaccharide‐induced myosin light chain phosphorylation in endothelial cells through inhibition of Rho/Rho kinase signaling [In Process Citation]. J Immunol 164: 6543‐6549, 2000.
 165. Etienne‐Manneville S, Hall A. Integrin‐mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. Cell 106: 489‐498, 2001.
 166. Faggioni R, Gatti S, Demitri MT, Delgado R, Echtenacher B, Gnocchi P, Heremans H, Ghezzi P. Role of xanthine oxidase and reactive oxygen intermediates in LPS‐ and TNF‐induced pulmonary edema. J Lab Clin Med 123: 394‐399, 1994.
 167. Fehrenbach H, Kasper M, Tschernig T, Pan T, Schuh D, Shannon JM, Muller M, Mason RJ. Keratinocyte growth factor‐induced hyperplasia of rat alveolar type II cells in vivo is resolved by differentiation into type I cells and by apoptosis. Eur Respir J 14: 534‐544, 1999.
 168. Feistritzer C, Mosheimer BA, Sturn DH, Riewald M, Patsch JR, Wiedermann CJ. Endothelial protein C receptor‐dependent inhibition of migration of human lymphocytes by protein C involves epidermal growth factor receptor. J Immunol 176: 1019‐1025, 2006.
 169. Feistritzer C, Riewald M. Endothelial barrier protection by activated protein C through PAR1‐dependent sphingosine 1‐phosphate receptor‐1 crossactivation. Blood 105: 3178‐3184, 2005.
 170. Feoktistov I, Goldstein AE, Biaggioni I. Cyclic AMP and protein kinase A stimulate Cdc42: Role of A(2) adenosine receptors in human mast cells. Mol Pharmacol 58: 903‐910, 2000.
 171. Ferkey DM, Kimelman D. GSK‐3: New thoughts on an old enzyme. Dev Biol 225: 471‐479, 2000.
 172. Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, Gale NW, Witzenrath M, Rosseau S, Suttorp N, Sobke A, Herrmann M, Preissner KT, Vajkoczy P, Augustin HG. Angiopoietin‐2 sensitizes endothelial cells to TNF‐alpha and has a crucial role in the induction of inflammation. Nat Med 12: 235‐239, 2006.
 173. Finigan JH, Boueiz A, Wilkinson E, Damico R, Skirball J, Pae HH, Damarla M, Hasan E, Pearse DB, Reddy SP, Grigoryev DN, Cheadle C, Esmon CT, Garcia JG, Hassoun PM. Activated protein C protects against ventilator‐induced pulmonary capillary leak. Am J Physiol 296: L1002‐L1011, 2009.
 174. Finigan JH, Dudek SM, Singleton PA, Chiang ET, Jacobson JR, Camp SM, Ye SQ, Garcia JG. Activated protein C mediates novel lung endothelial barrier enhancement: Role of sphingosine 1‐phosphate receptor transactivation. J Biol Chem 280: 17286‐17293, 2005.
 175. Fleming IN, Elliott CM, Buchanan FG, Downes CP, Exton JH. Ca2+/calmodulin‐dependent protein kinase II regulates Tiam1 by reversible protein phosphorylation. J Biol Chem 274: 12753‐12758, 1999.
 176. Fredholm BB, AP IJ, Jacobson KA, Klotz KN, Linden J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53: 527‐552, 2001.
 177. Frink M, Kaudel CP, Hildebrand F, Pape HC, Klempnauer J, Winkler M, Krettek C, van Griensven M. FTY720 improves survival after transient ischemia and reperfusion of the hind limbs. J Trauma 63: 263‐267, 2007.
 178. Fu P, Birukov KG. Oxidized phospholipids in control of inflammation and endothelial barrier. Transl Res 153: 166‐176, 2009.
 179. Fukata M, Kaibuchi K. Rho‐family GTPases in cadherin‐mediated cell‐cell adhesion. Nat Rev Mol Cell Biol 2: 887‐897, 2001.
 180. Fukata Y, Amano M, Kaibuchi K. Rho‐Rho‐kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non‐muscle cells. Trends Pharmacol Sci 22: 32‐39, 2001.
 181. Fukudome K, Esmon CT. Identification, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor. J Biol Chem 269: 26486‐26491, 1994.
 182. Fukuhara S, Sakurai A, Sano H, Yamagishi A, Somekawa S, Takakura N, Saito Y, Kangawa K, Mochizuki N. Cyclic AMP potentiates vascular endothelial cadherin‐mediated cell‐cell contact to enhance endothelial barrier function through an Epac‐Rap1 signaling pathway. Mol Cell Biol 25: 136‐146, 2005.
 183. Fukuyama T, Ogita H, Kawakatsu T, Inagaki M, Takai Y. Activation of Rac by cadherin through the c‐Src‐Rap1‐phosphatidylinositol 3‐kinase‐Vav2 pathway. Oncogene 25: 8‐19, 2006.
 184. Furst R, Brueckl C, Kuebler WM, Zahler S, Krotz F, Gorlach A, Vollmar AM, Kiemer AK. Atrial natriuretic peptide induces mitogen‐activated protein kinase phosphatase‐1 in human endothelial cells via Rac1 and NAD(P)H oxidase/Nox2‐activation. Circ Res 96: 43‐53, 2005.
 185. Galiacy S, Planus E, Lepetit H, Fereol S, Laurent V, Ware L, Isabey D, Matthay M, Harf A, and d'Ortho MP. Keratinocyte growth factor promotes cell motility during alveolar epithelial repair in vitro. Exp Cell Res 283: 215‐229, 2003.
 186. Galligan L, Livingstone W, Volkov Y, Hokamp K, Murphy C, Lawler M, Fukudome K, Smith O. Characterization of protein C receptor expression in monocytes. Br J Haematol 115: 408‐414, 2001.
 187. Gamble JR, Drew J, Trezise L, Underwood A, Parsons M, Kasminkas L, Rudge J, Yancopoulos G, Vadas MA. Angiopoietin‐1 is an antipermeability and anti‐inflammatory agent in vitro and targets cell junctions. Circ Res 87: 603‐607, 2000.
 188. Gao X, Kouklis P, Xu N, Minshall RD, Sandoval R, Vogel SM, Malik AB. Reversibility of increased microvessel permeability in response to VE‐cadherin disassembly. Am J Physiol 279: L1218‐L1225, 2000.
 189. Garcia‐Dorado D, Agullo L, Sartorio CL, Ruiz‐Meana M. Myocardial protection against reperfusion injury: The cGMP pathway. Thromb Haemost 101: 635‐642, 2009.
 190. Garcia JG, Davis HW, Patterson CE. Regulation of endothelial cell gap formation and barrier dysfunction: Role of myosin light chain phosphorylation. J Cell Physiol 163: 510‐522, 1995.
 191. Garcia JG, Liu F, Verin AD, Birukova A, Dechert MA, Gerthoffer WT, Bamberg JR, English D. Sphingosine 1‐phosphate promotes endothelial cell barrier integrity by Edg‐dependent cytoskeletal rearrangement. J Clin Invest 108: 689‐701, 2001.
 192. Garcia JG, Verin AD, Schaphorst K, Siddiqui R, Patterson CE, Csortos C, Natarajan V. Regulation of endothelial cell myosin light chain kinase by rho, cortactin, and p60(src). Am J Physiol 276: L989‐L998, 1999.
 193. Garcia JG, Wang P, Schaphorst KL, Becker PM, Borbiev T, Liu F, Birukova A, Jacobs K, Bogatcheva N, Verin AD. Critical involvement of p38 MAP kinase in pertussis toxin‐induced cytoskeletal reorganization and lung permeability. Faseb J 16: 1064‐1076, 2002.
 194. Gavard J, Gutkind JS. VEGF controls endothelial‐cell permeability by promoting the beta‐arrestin‐dependent endocytosis of VE‐cadherin. Nat Cell Biol 8: 1223‐1234, 2006.
 195. Geiger B, Bershadsky A. Assembly and mechanosensory function of focal contacts. Curr Opin Cell Biol 13: 584‐592, 2001.
 196. Geiger B, Bershadsky A, Pankov R, Yamada KM. Transmembrane crosstalk between the extracellular matrix–cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2: 793‐805, 2001.
 197. Geiser T. Mechanisms of alveolar epithelial repair in acute lung injury–a translational approach. Swiss Med Wkly 133: 586‐590, 2003.
 198. Gelfand RA, Frank HJ, Levin E, Pedram A. Brain and atrial natriuretic peptides bind to common receptors in brain capillary endothelial cells. Am J Physiol 261: E183‐E189, 1991.
 199. Gillis P, Savla U, Volpert OV, Jimenez B, Waters CM, Panos RJ, Bouck NP. Keratinocyte growth factor induces angiogenesis and protects endothelial barrier function. J Cell Sci 112(Pt 12): 2049‐2057, 1999.
 200. Goldberg PL, MacNaughton DE, Clements RT, Minnear FL, Vincent PA. p38 MAPK activation by TGF‐beta1 increases MLC phosphorylation and endothelial monolayer permeability. Am J Physiol 282: L146‐L154, 2002.
 201. Gong P, Angelini DJ, Yang S, Xia G, Cross AS, Mann D, Bannerman DD, Vogel SN, Goldblum SE. TLR4 signaling is coupled to SRC family kinase activation, tyrosine phosphorylation of zonula adherens proteins, and opening of the paracellular pathway in human lung microvascular endothelia. J Biol Chem 283: 13437‐13449, 2008.
 202. Goodman RB, Pugin J, Lee JS, Matthay MA. Cytokine‐mediated inflammation in acute lung injury. Cytokine Growth Factor Rev 14: 523‐535, 2003.
 203. Gotsch U, Borges E, Bosse R, Boggemeyer E, Simon M, Mossmann H, Vestweber D. VE‐cadherin antibody accelerates neutrophil recruitment in vivo. J Cell Sci 110(Pt 5): 583‐588, 1997.
 204. Griffin JH, Zlokovic B, Fernandez JA. Activated protein C: Potential therapy for severe sepsis, thrombosis, and stroke. Semin Hematol 39: 197‐205, 2002.
 205. Groeneveld AB. Vascular pharmacology of acute lung injury and acute respiratory distress syndrome. Vascul Pharmacol 39: 247‐256, 2002.
 206. Gropper MA, Wiener‐Kronish JP, Hashimoto S. Acute cardiogenic pulmonary edema. Clin Chest Med 15: 501‐515, 1994.
 207. Gunduz D, Hirche F, Hartel FV, Rodewald CW, Schafer M, Pfitzer G, Piper HM, Noll T. ATP antagonism of thrombin‐induced endothelial barrier permeability. Cardiovasc Res 59: 470‐478, 2003.
 208. Guo J, Yi ES, Havill AM, Sarosi I, Whitcomb L, Yin S, Middleton SC, Piguet P, Ulich TR. Intravenous keratinocyte growth factor protects against experimental pulmonary injury. Am J Physiol 275: L800‐L805, 1998.
 209. Guo Y, Singleton PA, Rowshan A, Gucek M, Cole RN, Graham DR, van Eyk JE, Garcia JG. Quantitative proteomics analysis of human endothelial cell membrane rafts: Evidence of MARCKS and MRP regulation in the sphingosine 1‐phosphate‐induced barrier enhancement. Mol Cell Proteomics 6: 689‐696, 2007.
 210. Gupta MP, Ober MD, Patterson C, Al‐Hassani M, Natarajan V, Hart CM. Nitric oxide attenuates H(2)O(2)‐induced endothelial barrier dysfunction: Mechanisms of protection. Am J Physiol 280: L116‐L126, 2001.
 211. Hait NC, Oskeritzian CA, Paugh SW, Milstien S, Spiegel S. Sphingosine kinases, sphingosine 1‐phosphate, apoptosis and diseases. Biochim Biophys Acta 1758: 2016‐2026, 2006.
 212. Haitsma JJ, Papadakos PJ, Lachmann B. Surfactant therapy for acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care 10: 18‐22, 2004.
 213. Hamacher J, Lucas R, Lijnen HR, Buschke S, Dunant Y, Wendel A, Grau GE, Suter PM, Ricou B. Tumor necrosis factor‐alpha and angiostatin are mediators of endothelial cytotoxicity in bronchoalveolar lavages of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 166: 651‐656, 2002.
 214. Hammerschmidt S, Schiller J, Kuhn H, Meybaum M, Gessner C, Sandvoss T, Arnold K, Wirtz H. Influence of tidal volume on pulmonary NO release, tissue lipid peroxidation and surfactant phospholipids. Biochim Biophys Acta 1639: 17‐26, 2003.
 215. Hanada M, Feng J, Hemmings BA. Structure, regulation and function of PKB/AKT–a major therapeutic target. Biochim Biophys Acta 1697: 3‐16, 2004.
 216. Hanahan D. Signaling vascular morphogenesis and maintenance. Science 277: 48‐50, 1997.
 217. Hantschel O, Superti‐Furga G. Regulation of the c‐Abl and Bcr‐Abl tyrosine kinases. Nat Rev Mol Cell Biol 5: 33‐44, 2004.
 218. Hata AN, Breyer RM. Pharmacology and signaling of prostaglandin receptors: Multiple roles in inflammation and immune modulation. Pharmacol Ther 103: 147‐166, 2004.
 219. Hazama A, Hayashi S, Okada Y. Cell surface measurements of ATP release from single pancreatic beta cells using a novel biosensor technique. Pflugers Arch 437: 31‐35, 1998.
 220. He P, Curry FE. Differential actions of cAMP on endothelial [Ca2+]i and permeability in microvessels exposed to ATP. Am J Physiol 265: H1019‐H1023, 1993.
 221. He P, Zeng M, Curry FE. Dominant role of cAMP in regulation of microvessel permeability. Am J Physiol Heart Circ Physiol 278: H1124‐H1133, 2000.
 222. Held HD, Uhlig S. Mechanisms of endotoxin‐induced airway and pulmonary vascular hyperreactivity in mice. Am J Respir Crit Care Med 162: 1547‐1552, 2000.
 223. Herbrand U, Ahmadian MR. p190‐RhoGAP as an integral component of the Tiam1/Rac1‐induced downregulation of Rho. Biol Chem 387: 311‐317, 2006.
 224. Hla T. Signaling and biological actions of sphingosine 1‐phosphate. Pharmacol Res 47: 401‐407, 2003.
 225. Hla T, Lee MJ, Ancellin N, Paik JH, Kluk MJ. Lysophospho‐lipids–receptor revelations. Science 294: 1875‐1878, 2001.
 226. Hla T, Maciag T. An abundant transcript induced in differentiating human endothelial cells encodes a polypeptide with structural similarities to G‐protein‐coupled receptors. J Biol Chem 265: 9308‐9313, 1990.
 227. Holinstat M, Knezevic N, Broman M, Samarel AM, Malik AB, Mehta D. Suppression of RhoA activity by focal adhesion kinase‐induced activation of p190RhoGAP: Role in regulation of endothelial permeability. J Biol Chem 281: 2296‐2305, 2006.
 228. Holinstat M, Mehta D, Kozasa T, Minshall RD, Malik AB. Protein kinase Calpha‐induced p115RhoGEF phosphorylation signals endothelial cytoskeletal rearrangement. J Biol Chem 278: 28793‐28798, 2003.
 229. Hordijk PL, Anthony E, Mul FP, Rientsma R, Oomen LC, Roos D. Vascular‐endothelial‐cadherin modulates endothelial monolayer permeability. J Cell Sci 112(Pt 12): 1915‐1923, 1999.
 230. Howard LS, Morrell NW. New therapeutic agents for pulmonary vascular disease. Paediatr Respir Rev 6: 285‐291, 2005.
 231. Hu G, Ye RD, Dinauer MC, Malik AB, Minshall RD. Neutrophil caveolin‐1 expression contributes to mechanism of lung inflammation and injury. Am J Physiol 294: L178‐L186, 2008.
 232. Huang F, Subbaiah PV, Holian O, Zhang J, Johnson A, Gertzberg N, Lum H. Lysophosphatidylcholine increases endothelial permeability: Role of PKCalpha and RhoA cross talk. Am J Physiol 289: L176‐L185, 2005.
 233. Huang SK, Wettlaufer SH, Hogaboam CM, Aronoff DM, Peters‐Golden M. Prostaglandin E(2) inhibits collagen expression and proliferation in patient‐derived normal lung fibroblasts via E prostanoid 2 receptor and cAMP signaling. Am J Physiol Lung Cell Mol Physiol 229: L405‐L413, 2007.
 234. Hurst VI, Goldberg PL, Minnear FL, Heimark RL, Vincent PA. Rearrangement of adherens junctions by transforming growth factor‐ beta1: Role of contraction. Am J Physiol 276: L582‐L595, 1999.
 235. Idell S, Koenig KB, Fair DS, Martin TR, McLarty J, Maunder RJ. Serial abnormalities of fibrin turnover in evolving adult respiratory distress syndrome. Am J Physiol 261: L240‐L248, 1991.
 236. Ikeda M, Kito H, Sumpio BE. Phosphatidylinositol‐3 kinase dependent MAP kinase activation via p21ras in endothelial cells exposed to cyclic strain. Biochem Biophys Res Commun 257: 668‐671, 1999.
 237. Imai Y, Kuba K, Neely GG, Yaghubian‐Malhami R, Perkmann T, van Loo G, Ermolaeva M, Veldhuizen R, Leung YH, Wang H, Liu H, Sun Y, Pasparakis M, Kopf M, Mech C, Bavari S, Peiris JS, Slutsky AS, Akira S, Hultqvist M, Holmdahl R, Nicholls J, Jiang C, Binder CJ, Penninger JM. Identification of oxidative stress and Toll‐like receptor 4 signaling as a key pathway of acute lung injury. Cell 133: 235‐249, 2008.
 238. Imamura H, Tanaka K, Hihara T, Umikawa M, Kamei T, Takahashi K, Sasaki T, Takai Y. Bni1p and Bnr1p: Downstream targets of the Rho family small G‐proteins which interact with profilin and regulate actin cytoskeleton in Saccharomyces cerevisiae. EMBO J 16: 2745‐2755, 1997.
 239. Imamura T, Ohnuma N, Iwasa F, Furuya M, Hayashi Y, Inomata N, Ishihara T, Noguchi T. Protective effect of alpha‐human atrial natriuretic polypeptide (alpha‐hANP) on chemical‐induced pulmonary edema. Life Sci 42: 403‐414, 1988.
 240. Ingber DE. Tensegrity: The architectural basis of cellular mechanotransduction. Annu Rev Physiol 59: 575‐599, 1997.
 241. Ingber DE. Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci 116: 1157‐1173, 2003.
 242. Ingram AJ, James L, Ly H, Thai K, Scholey JW. Stretch activation of jun N‐terminal kinase/stress‐activated protein kinase in mesangial cells. Kidney Int 58: 1431‐1439, 2000.
 243. Irwin DC, Rhodes J, Baker DC, Nelson SE, Tucker A. Atrial natriuretic peptide blockade exacerbates high altitude pulmonary edema in endotoxin‐primed rats. High Alt Med Biol 2: 349‐360, 2001.
 244. Irwin DC, Tissot van Patot MC, Tucker A, Bowen R. Direct ANP inhibition of hypoxia‐induced inflammatory pathways in pulmonary microvascular and macrovascular endothelial monolayers. Am J Physiol 288: L849‐L859, 2005.
 245. Isagawa T, Mukai H, Oishi K, Taniguchi T, Hasegawa H, Kawamata T, Tanaka C, Ono Y. Dual effects of PKNalpha and protein kinase C on phosphorylation of tau protein by glycogen synthase kinase‐3beta. Biochem Biophys Res Commun 273: 209‐212, 2000.
 246. Isermann B, Vinnikov IA, Madhusudhan T, Herzog S, Kashif M, Blautzik J, Corat MA, Zeier M, Blessing E, Oh J, Gerlitz B, Berg DT, Grinnell BW, Chavakis T, Esmon CT, Weiler H, Bierhaus A, Nawroth PP. Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis. Nat Med 13: 1349‐1358, 2007.
 247. Iwasaki H, Eguchi S, Ueno H, Marumo F, Hirata Y. Mechanical stretch stimulates growth of vascular smooth muscle cells via epidermal growth factor receptor. Am J Physiol Heart Circ Physiol 278: H521‐H529, 2000.
 248. Jacobson JR, Barnard JW, Grigoryev DN, Ma SF, Tuder RM, Garcia JG. Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury. Am J Physiol 288: L1026‐L1032, 2005.
 249. Jacobson JR, Dudek SM, Birukov KG, Ye SQ, Grigoryev DN, Girgis RE, Garcia JG. Cytoskeletal activation and altered gene expression in endothelial barrier regulation by simvastatin. Am J Respir Cell Mol Biol 30: 662‐670, 2004.
 250. Jacobson JR, Dudek SM, Singleton PA, Kolosova IA, Verin AD, Garcia JG. Endothelial cell barrier enhancement by ATP is mediated by the small GTPase Rac and cortactin. Am J Physiol 291: L289‐L295, 2006.
 251. Jacobson JR, Garcia JG. Novel therapies for microvascular permeability in sepsis. Curr Drug Targets 8: 509‐514, 2007.
 252. Jacobson KA, Gao ZG. Adenosine receptors as therapeutic targets. Nat Rev Drug Discov 5: 247‐264, 2006.
 253. Jayle C, Corbi P, Eugene M, Carretier M, Hebrard W, Menet E, Hauet T. Beneficial effect of polyethylene glycol in lung preservation: Early evaluation by proton nuclear magnetic resonance spectroscopy. Ann Thorac Surg 76: 896‐902, 2003.
 254. Jiang XW, Kambara K, Gotoh N, Nishigaki K, Fujiwara H. Effects of low‐dose Beraprost sodium, a stable prostaglandin I2 analogue, on reperfusion injury to rabbit lungs. Am J Respir Crit Care Med 158: 1669‐1675, 1998.
 255. Joberty G, Petersen C, Gao L, Macara IG. The cell‐polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat Cell Biol 2: 531‐539, 2000.
 256. Johnson A, Phillips P, Hocking D, Tsan MF, Ferro T. Protein kinase inhibitor prevents pulmonary edema in response to H2O2. Am J Physiol 256: H1012‐H1022, 1989.
 257. Joshi HC. Microtubule dynamics in living cells. Curr Opin Cell Biol 10: 35‐44, 1998.
 258. Kaibuchi K, Kuroda S, Amano M. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. Annu Rev Biochem 68: 459‐486, 1999.
 259. Kaibuchi K, Kuroda S, Fukata M, Nakagawa M. Regulation of cadherin‐mediated cell‐cell adhesion by the Rho family GTPases. Curr Opin Cell Biol 11: 591‐596, 1999.
 260. Kalyanaraman B. Nitrated lipids: A class of cell‐signaling molecules. Proc Natl Acad Sci U S A 101: 11527‐11528, 2004.
 261. Kano Y, Katoh K, Fujiwara K. Lateral zone of cell‐cell adhesion as the major fluid shear stress‐related signal transduction site. Circ Res 86: 425‐433, 2000.
 262. Kapur S, Kupfer Y, Tessler S. Recombinant human activated protein C for severe sepsis. N Engl J Med 345: 219‐220; author reply 220‐211, 2001.
 263. Karmpaliotis D, Kirtane AJ, Ruisi CP, Polonsky T, Malhotra A, Talmor D, Kosmidou I, Jarolim P, de Lemos JA, Sabatine MS, Gibson CM, Morrow D. Diagnostic and prognostic utility of brain natriuretic Peptide in subjects admitted to the ICU with hypoxic respiratory failure due to noncardiogenic and cardiogenic pulmonary edema. Chest 131: 964‐971, 2007.
 264. Kasseckert SA, Schafer C, Kluger A, Gligorievski D, Tillmann J, Schluter KD, Noll T, Sauer H, Piper HM, Abdallah Y. Stimulation of cGMP signalling protects coronary endothelium against reperfusion‐induced intercellular gap formation. Cardiovasc Res 83: 381‐387, 2009.
 265. Kato M, Mrksich M. Using model substrates to study the dependence of focal adhesion formation on the affinity of integrin‐ligand complexes. Biochemistry 43: 2699‐2707, 2004.
 266. Katso R, Okkenhaug K, Ahmadi K, White S, Timms J, Waterfield MD. Cellular function of phosphoinositide 3‐kinases: Implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol 17: 615‐675, 2001.
 267. Katsumi A, Milanini J, Kiosses WB, del Pozo MA, Kaunas R, Chien S, Hahn KM, Schwartz MA. Effects of cell tension on the small GTPase Rac. J Cell Biol 158: 153‐164, 2002.
 268. Katsumi A, Orr AW, Tzima E, Schwartz MA. Integrins in mechanotransduction. J Biol Chem 279: 12001‐12004, 2004.
 269. Kaunas R, Nguyen P, Usami S, Chien S. Cooperative effects of Rho and mechanical stretch on stress fiber organization. Proc Natl Acad Sci U S A 102: 15895‐15900, 2005.
 270. Kevil CG, Okayama N, Trocha SD, Kalogeris TJ, Coe LL, Specian RD, Davis CP, Alexander JS. Expression of zonula occludens and adherens junctional proteins in human venous and arterial endothelial cells: Role of occludin in endothelial solute barriers. Microcirculation 5: 197‐210, 1998.
 271. Kiemer AK, Hartung T, Vollmar AM. cGMP‐mediated inhibition of TNF‐alpha production by the atrial natriuretic peptide in murine macrophages. J Immunol 165: 175‐181, 2000.
 272. Kiemer AK, Weber NC, Furst R, Bildner N, Kulhanek‐Heinze S, Vollmar AM. Inhibition of p38 MAPK activation via induction of MKP‐1: Atrial natriuretic peptide reduces TNF‐alpha‐induced actin polymerization and endothelial permeability. Circ Res 90: 874‐881, 2002.
 273. Kiosses WB, Daniels RH, Otey C, Bokoch GM, Schwartz MA. A role for p21‐activated kinase in endothelial cell migration. J Cell Biol 147: 831‐844, 1999.
 274. Kline JN, Cowden JD, Hunninghake GW, Schutte BC, Watt JL, Wohlford‐Lenane CL, Powers LS, Jones MP, Schwartz DA. Variable airway responsiveness to inhaled lipopolysaccharide. Am J Respir Crit Care Med 160: 297‐303, 1999.
 275. Klinger JR, Warburton R, Carino GP, Murray J, Murphy C, Napier M, Harrington EO. Natriuretic peptides differentially attenuate thrombin‐induced barrier dysfunction in pulmonary microvascular endothelial cells. Exp Cell Res 312: 401‐410, 2006.
 276. Kokot F, Klimek D, Wiecek A, Kuczera M. Atrial natriuretic peptide and arginine‐vasopressin secretion in patients with active renal stone disease. Int Urol Nephrol 30: 357‐365, 1998.
 277. Koksel O, Yildirim C, Tiftik RN, Kubat H, Tamer L, Cinel L, Kaplan MB, Degirmenci U, Ozdulger A, Buyukafsar K. Rho‐kinase (ROCK‐1 and ROCK‐2) upregulation in oleic acid‐induced lung injury and its restoration by Y‐27632. Eur J Pharmacol 510: 135‐142, 2005.
 278. Koller KJ, Goeddel DV. Molecular biology of the natriuretic peptides and their receptors. Circulation 86: 1081‐1088, 1992.
 279. Kolosova IA, Mirzapoiazova T, Adyshev D, Usatyuk P, Romer LH, Jacobson JR, Natarajan V, Pearse DB, Garcia JG, Verin AD. Signaling pathways involved in adenosine triphosphate‐induced endothelial cell barrier enhancement. Circ Res 97: 115‐124, 2005.
 280. Kolosova IA, Mirzapoiazova T, Moreno‐Vinasco L, Sammani S, Garcia JG, Verin AD. Protective effect of purinergic agonist ATPgammaS against acute lung injury. Am J Physiol 294: L319‐L324, 2008.
 281. Konduri GG, Bakhutashvili I, Frenn R, Chandrasekhar I, Jacobs ER, Khanna AK. P2Y purine receptor responses and expression in the pulmonary circulation of juvenile rabbits. Am J Physiol Heart Circ Physiol 287: H157‐H164, 2004.
 282. Konstantoulaki M, Kouklis P, Malik AB. Protein kinase C modifications of VE‐cadherin, p120, and beta‐catenin contribute to endothelial barrier dysregulation induced by thrombin. Am J Physiol 285: L434‐L442, 2003.
 283. Kooistra MR, Corada M, Dejana E, Bos JL. Epac1 regulates integrity of endothelial cell junctions through VE‐cadherin. FEBS Lett 579: 4966‐4972, 2005.
 284. Koss M, Pfeiffer GR, II, Wang Y, Thomas ST, Yerukhimovich M, Gaarde WA, Doerschuk CM, Wang Q. Ezrin/radixin/moesin proteins are phosphorylated by TNF‐alpha and modulate permeability increases in human pulmonary microvascular endothelial cells. J Immunol 176: 1218‐1227, 2006.
 285. Kouklis P, Konstantoulaki M, Vogel S, Broman M, Malik AB. Cdc42 regulates the restoration of endothelial barrier function. Circ Res 94: 159‐166, 2004.
 286. Kovacs EM, Ali RG, McCormack AJ, Yap AS. E‐cadherin homophilic ligation directly signals through Rac and phosphatidylinositol 3‐kinase to regulate adhesive contacts. J Biol Chem 277: 6708‐6718, 2002.
 287. Krendel M, Zenke FT, Bokoch GM. Nucleotide exchange factor GEF‐H1 mediates cross‐talk between microtubules and the actin cytoskeleton. Nat Cell Biol 4: 294‐301, 2002.
 288. Krump‐Konvalinkova V, Yasuda S, Rubic T, Makarova N, Mages J, Erl W, Vosseler C, Kirkpatrick CJ, Tigyi G, Siess W. Stable knock‐down of the sphingosine 1‐phosphate receptor S1P1 influences multiple functions of human endothelial cells. Arterioscler Thromb Vasc Biol 25: 546‐552, 2005.
 289. Kuijk LM, Beekman JM, Koster J, Waterham HR, Frenkel J, Coffer PJ. HMG‐CoA reductase inhibition induces IL‐1beta release through Rac1/PI3K/PKB‐dependent caspase‐1 activation. Blood 112: 3563‐3573, 2008.
 290. Kumar CC. Signaling by integrin receptors. Oncogene 17: 1365‐1373, 1998.
 291. Kurimoto N, Nan YS, Chen ZY, Feng GG, Komatsu T, Kandatsu N, Ko J, Kawai N, Ishikawa N. Effects of specific signal transduction inhibitors on increased permeability across rat endothelial monolayers induced by neuropeptide Y or VEGF. Am J Physiol Heart Circ Physiol 287: H100‐H106, 2004.
 292. Ladetzki‐Baehs K, Keller M, Kiemer AK, Koch E, Zahler S, Wendel A, Vollmar AM. Atrial natriuretic peptide, a regulator of nuclear factor‐kappaB activation in vivo. Endocrinology 148: 332‐336, 2007.
 293. Lai A, Frishman WH. Rho‐kinase inhibition in the therapy of cardiovascular disease. Cardiol Rev 13: 285‐292, 2005.
 294. Lambeng N, Wallez Y, Rampon C, Cand F, Christe G, Gulino‐Debrac D, Vilgrain I, Huber P. Vascular endothelial‐cadherin tyrosine phosphorylation in angiogenic and quiescent adult tissues. Circ Res 96: 384‐391, 2005.
 295. Lambert D, O'Neill CA, Padfield PJ. Methyl‐beta‐cyclodextrin increases permeability of Caco‐2 cell monolayers by displacing specific claudins from cholesterol rich domains associated with tight junctions. Cell Physiol Biochem 20: 495‐506, 2007.
 296. Lampugnani MG, Corada M, Andriopoulou P, Esser S, Risau W, Dejana E. Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells. J Cell Sci 110(Pt 17): 2065‐2077, 1997.
 297. Lampugnani MG, Giorgi M, Gaboli M, Dejana E, Marchisio PC. Endothelial cell motility, integrin receptor clustering, and microfilament organization are inhibited by agents that increase intracellular cAMP. Lab Invest 63: 521‐531, 1990.
 298. Lampugnani MG, Resnati M, Dejana E, Marchisio PC. The role of integrins in the maintenance of endothelial monolayer integrity. J Cell Biol 112: 479‐490, 1991.
 299. Lampugnani MG, Zanetti A, Breviario F, Balconi G, Orsenigo F, Corada M, Spagnuolo R, Betson M, Braga V, Dejana E. VE‐cadherin regulates endothelial actin activating Rac and increasing membrane association of Tiam. Mol Biol Cell 13: 1175‐1189, 2002.
 300. Lang JD, McArdle PJ, O'Reilly PJ, Matalon S. Oxidant‐antioxidant balance in acute lung injury. Chest 122: 314S‐320S, 2002.
 301. Lang P, Gesbert F, Delespine‐Carmagnat M, Stancou R, Pouchelet M, Bertoglio J. Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes. EMBO J 15: 510‐519, 1996.
 302. Lazarowski ER, Boucher RC, Harden TK. Mechanisms of release of nucleotides and integration of their action as P2X‐ and P2Y‐receptor activating molecules. Mol Pharmacol 64: 785‐795, 2003.
 303. Lee JF, Ozaki H, Zhan X, Wang E, Hla T, Lee MJ. Sphingosine‐1‐phosphate signaling regulates lamellipodia localization of cortactin complexes in endothelial cells. Histochem Cell Biol 126: 297‐304, 2006.
 304. Lee JF, Zeng Q, Ozaki H, Wang L, Hand AR, Hla T, Wang E, Lee MJ. Dual roles of tight junction‐associated protein, zonula occludens‐1, in sphingosine 1‐phosphate‐mediated endothelial chemotaxis and barrier integrity. J Biol Chem 281: 29190‐29200, 2006.
 305. Lee MJ, Evans M, Hla T. The inducible G protein‐coupled receptor edg‐1 signals via the G(i)/mitogen‐activated protein kinase pathway. J Biol Chem 271: 11272‐11279, 1996.
 306. Lee MJ, Thangada S, Claffey KP, Ancellin N, Liu CH, Kluk M, Volpi M, Sha'afi RI, Hla T. Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine‐1‐phosphate. Cell 99: 301‐312, 1999.
 307. Lee MJ, Van Brocklyn JR, Thangada S, Liu CH, Hand AR, Menzeleev R, Spiegel S, Hla T. Sphingosine‐1‐phosphate as a ligand for the G protein‐coupled receptor EDG‐1. Science 279: 1552‐1555, 1998.
 308. Lee SW, Kim WJ, Jun HO, Choi YK, Kim KW. Angiopoietin‐1 reduces vascular endothelial growth factor‐induced brain endothelial permeability via upregulation of ZO‐2. Int J Mol Med 23: 279‐284, 2009.
 309. Lee TY, Gotlieb AI. Microfilaments and microtubules maintain endothelial integrity. Microsc Res Tech 60: 115‐127, 2003.
 310. Li J, O'Connor K L, Cheng X, Mei FC, Uchida T, Townsend CM, Jr, Evers BM. Cyclic Amp‐stimulated neurotensin secretion is mediated through Rap1 downstream of both Epac and Pka signaling pathways. Mol Endocrinol 2006.
 311. Li Y, Wu Y, Wang Z, Zhang XH, Wu WK. Fasudil attenuates lipopolysaccharide‐induced acute lung injury in mice through the Rho/Rho kinase pathway. Med Sci Monit 16: BR112‐BR118, 2010.
 312. Liang TW, DeMarco RA, Mrsny RJ, Gurney A, Gray A, Hooley J, Aaron HL, Huang A, Klassen T, Tumas DB, Fong S. Characterization of huJAM: Evidence for involvement in cell‐cell contact and tight junction regulation. Am J Physiol Cell Physiol 279: C1733‐C1743, 2000.
 313. Liaw PC, Neuenschwander PF, Smirnov MD, Esmon CT. Mechanisms by which soluble endothelial cell protein C receptor modulates protein C and activated protein C function. J Biol Chem 275: 5447‐5452, 2000.
 314. Liu F, Schaphorst KL, Verin AD, Jacobs K, Birukova A, Day RM, Bogatcheva N, Bottaro DP, Garcia JG. Hepatocyte growth factor enhances endothelial cell barrier function and cortical cytoskeletal rearrangement: Potential role of glycogen synthase kinase‐3beta. Faseb J 16: 950‐962, 2002.
 315. Liu F, Verin AD, Borbiev T, Garcia JG. Role of cAMP‐dependent protein kinase A activity in endothelial cell cytoskeleton rearrangement. Am J Physiol 280: L1309‐L1317, 2001.
 316. Liu HB, Cui NQ, Wang Q, Li DH, Xue XP. Sphingosine‐1‐phosphate and its analogue FTY720 diminish acute pulmonary injury in rats with acute necrotizing pancreatitis. Pancreas 36: e10‐e15, 2008.
 317. Liu KD, Levitt J, Zhuo H, Kallet RH, Brady S, Steingrub J, Tidswell M, Siegel MD, Soto G, Peterson MW, Chesnutt MS, Phillips C, Weinacker A, Thompson BT, Eisner MD, Matthay MA. Randomized clinical trial of activated protein C for the treatment of acute lung injury. Am J Respir Crit Care Med 178: 618‐623, 2008.
 318. Liu M, Qin Y, Liu J, Tanswell AK, Post M. Mechanical strain induces pp60src activation and translocation to cytoskeleton in fetal rat lung cells. J Biol Chem 271: 7066‐7071, 1996.
 319. Liu Y, Nusrat A, Schnell FJ, Reaves TA, Walsh S, Pochet M, Parkos CA. Human junction adhesion molecule regulates tight junction resealing in epithelia. J Cell Sci 113(Pt 13): 2363‐2374, 2000.
 320. Lockinger A, Schutte H, Walmrath D, Seeger W, Grimminger F. Protection against gas exchange abnormalities by pre‐aerosolized PGE1, iloprost and nitroprusside in lung ischemia‐reperfusion. Transplantation 71: 185‐193, 2001.
 321. Lofton CE, Baron DA, Heffner JE, Currie MG, Newman WH. Atrial natriuretic peptide inhibits oxidant‐induced increases in endothelial permeability. J Mol Cell Cardiol 23: 919‐927, 1991.
 322. Lorenowicz MJ, van Gils J, de Boer M, Hordijk PL, Fernandez‐Borja M. Epac1‐Rap1 signaling regulates monocyte adhesion and chemotaxis. J Leukoc Biol 80: 1542‐1552, 2006.
 323. Louzier V, Eddahibi S, Raffestin B, Deprez I, Adam M, Levame M, Eloit M, Adnot S. Adenovirus‐mediated atrial natriuretic protein expression in the lung protects rats from hypoxia‐induced pulmonary hypertension. Hum Gene Ther 12: 503‐513, 2001.
 324. Lovgren AK, Jania LA, Hartney JM, Parsons KK, Audoly LP, Fitzgerald GA, Tilley SL, Koller BH. COX‐2‐derived prostacyclin protects against bleomycin‐induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 291: L144‐L156, 2006.
 325. Lucas R, Garcia I, Donati YR, Hribar M, Mandriota SJ, Giroud C, Buurman WA, Fransen L, Suter PM, Nunez G, Pepper MS, Grau GE. Both TNF receptors are required for direct TNF‐mediated cytotoxicity in microvascular endothelial cells. Eur J Immunol 28: 3577‐3586, 1998.
 326. Lucas R, Verin AD, Black SM, Catravas JD. Regulators of endothelial and epithelial barrier integrity and function in acute lung injury. Biochem Pharmacol 77: 1763‐1772, 2009.
 327. Lum H, Jaffe HA, Schulz IT, Masood A, RayChaudhury A, Green RD. Expression of PKA inhibitor (PKI) gene abolishes cAMP‐mediated protection to endothelial barrier dysfunction. Am J Physiol 277: C580‐C588, 1999.
 328. Lum H, Roebuck KA. Oxidant stress and endothelial cell dysfunction. Am J Physiol Cell Physiol 280: C719‐C741, 2001.
 329. Luo J, Borgens R, Shi R. Polyethylene glycol immediately repairs neuronal membranes and inhibits free radical production after acute spinal cord injury. J Neurochem 83: 471‐480, 2002.
 330. Luo J, Borgens R, Shi R. Polyethylene glycol improves function and reduces oxidative stress in synaptosomal preparations following spinal cord injury. J Neurotrauma 21: 994‐1007, 2004.
 331. Ma Z, Li J, Yang L, Mu Y, Xie W, Pitt B, Li S. Inhibition of LPS‐ and CpG DNA‐induced TNF‐alpha response by oxidized phospholipids. Am J Physiol 286: L808‐L816, 2004.
 332. Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM‐kinase. Science 285: 895‐898, 1999.
 333. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD. Angiopoietin‐2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277: 55‐60, 1997.
 334. Makiuchi A, Yamaura K, Mizuno S, Matsumoto K, Nakamura T, Amano J, Ito K. Hepatocyte growth factor prevents pulmonary ischemia‐reperfusion injury in mice. J Heart Lung Transplant 26: 935‐943, 2007.
 335. Malek AM, Jiang L, Lee I, Sessa WC, Izumo S, Alper SL. Induction of nitric oxide synthase mRNA by shear stress requires intracellular calcium and G‐protein signals and is modulated by PI 3 kinase. Biochem Biophys Res Commun 254: 231‐242, 1999.
 336. Malliri A, van Es S, Huveneers S, Collard JG. The Rac exchange factor Tiam1 is required for the establishment and maintenance of cadherin‐based adhesions. J Biol Chem 279: 30092‐30098, 2004.
 337. Mandala S, Hajdu R, Bergstrom J, Quackenbush E, Xie J, Milligan J, Thornton R, Shei GJ, Card D, Keohane C, Rosenbach M, Hale J, Lynch CL, Rupprecht K, Parsons W, Rosen H. Alteration of lymphocyte trafficking by sphingosine‐1‐phosphate receptor agonists. Science 296: 346‐349, 2002.
 338. Maniatis NA, Orfanos SE. The endothelium in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care 14: 22‐30, 2008.
 339. Matsumoto K, Nakamura T. Emerging multipotent aspects of hepatocyte growth factor. J Biochem (Tokyo) 119: 591‐600, 1996.
 340. Matthay MA. Treatment of acute lung injury: Clinical and experimental studies. Proc Am Thorac Soc 5: 297‐299, 2008.
 341. Matthay MA, Fukuda N, Frank J, Kallet R, Daniel B, Sakuma T. Alveolar epithelial barrier. Role in lung fluid balance in clinical lung injury. Clin Chest Med 21: 477‐490, 2000.
 342. Matthay MA, Robriquet L, Fang X. Alveolar epithelium: Role in lung fluid balance and acute lung injury. Proc Am Thorac Soc 2: 206‐213, 2005.
 343. Mazaki Y, Hashimoto S, Okawa K, Tsubouchi A, Nakamura K, Yagi R, Yano H, Kondo A, Iwamatsu A, Mizoguchi A, Sabe H. An ADP‐ribosylation factor GTPase‐activating protein Git2‐ short/KIAA0148 is involved in subcellular localization of paxillin and actin cytoskeletal organization. Mol Biol Cell 12: 645‐662, 2001.
 344. McAuley DF, Frank JA, Fang X, Matthay MA. Clinically relevant concentrations of beta2‐adrenergic agonists stimulate maximal cyclic adenosine monophosphate‐dependent airspace fluid clearance and decrease pulmonary edema in experimental acid‐induced lung injury. Crit Care Med 32: 1470‐1476, 2004.
 345. McCaffrey G, Staatz WD, Quigley CA, Nametz N, Seelbach MJ, Campos CR, Brooks TA, Egleton RD, Davis TP. Tight junctions contain oligomeric protein assembly critical for maintaining blood‐brain barrier integrity in vivo. J Neurochem 103: 2540‐2555, 2007.
 346. McVerry BJ, Peng X, Hassoun PM, Sammani S, Simon BA, Garcia JG. Sphingosine 1‐phosphate reduces vascular leak in murine and canine models of acute lung injury. Am J Respir Crit Care Med 170: 987‐993, 2004.
 347. Mehta D, Konstantoulaki M, Ahmmed GU, Malik AB. Sphingosine 1‐phosphate‐induced mobilization of intracellular Ca2+ mediates rac activation and adherens junction assembly in endothelial cells. J Biol Chem 280: 17320‐17328, 2005.
 348. Mehta D, Malik AB. Signaling mechanisms regulating endothelial permeability. Physiol Rev 86: 279‐367, 2006.
 349. Mehta D, Rahman A, Malik AB. Protein kinase C‐alpha signals rho‐guanine nucleotide dissociation inhibitor phosphorylation and rho activation and regulates the endothelial cell barrier function. J Biol Chem 276: 22614‐22620, 2001.
 350. Mehta D, Tiruppathi C, Sandoval R, Minshall RD, Holinstat M, Malik AB. Modulatory role of focal adhesion kinase in regulating human pulmonary arterial endothelial barrier function. J Physiol 539: 779‐789, 2002.
 351. Mei FC, Qiao J, Tsygankova OM, Meinkoth JL, Quilliam LA, Cheng X. Differential signaling of cyclic AMP: Opposing effects of exchange protein directly activated by cyclic AMP and cAMP‐dependent protein kinase on protein kinase B activation. J Biol Chem 277: 11497‐11504, 2002.
 352. Mei SH, McCarter SD, Deng Y, Parker CH, Liles WC, Stewart DJ. Prevention of LPS‐induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Med 4: e269, 2007.
 353. Meyer P, Prodromou C, Hu B, Vaughan C, Roe SM, Panaretou B, Piper PW, Pearl LH. Structural and functional analysis of the middle segment of hsp90: Implications for ATP hydrolysis and client protein and cochaperone interactions. Molecular cell 11: 647‐658, 2003.
 354. Michel CC, Curry FE. Microvascular permeability. Physiol Rev 79: 703‐761, 1999.
 355. Miki T, Fleming TP, Bottaro DP, Rubin JS, Ron D, Aaronson SA. Expression cDNA cloning of the KGF receptor by creation of a transforming autocrine loop. Science 251: 72‐75, 1991.
 356. Millard TH, Machesky LM. The Wiskott‐Aldrich syndrome protein (WASP) family. Trends Biochem Sci 26: 198‐199, 2001.
 357. Minhas N, Xue M, Fukudome K, Jackson CJ. Activated protein C utilizes the angiopoietin/Tie2 axis to promote endothelial barrier function. Faseb J 24: 873‐881, 2010.
 358. Minnear FL, Connell RS. Increased permeability of the capillary‐alveolar barriers in neurogenic pulmonary edema (NPE). Microvasc Res 22: 345‐366, 1981.
 359. Minshall RD, Sessa WC, Stan RV, Anderson RG, Malik AB. Caveolin regulation of endothelial function. Am J Physiol 285: L1179‐L1183, 2003.
 360. Minshall RD, Tiruppathi C, Vogel SM, Malik AB. Vesicle formation and trafficking in endothelial cells and regulation of endothelial barrier function. Histochem Cell Biol 117: 105‐112, 2002.
 361. Mirzapoiazova T, Kolosova IA, Moreno L, Sammani S, Garcia JG, Verin AD. Suppression of endotoxin‐induced inflammation by taxol. Eur Respir J 30: 429‐435, 2007.
 362. Mitaka C, Hirata Y, Nagura T, Sakanishi N, Tsunoda Y, Amaha K. Plasma alpha‐human atrial natriuretic peptide concentration in patients with acute lung injury. Am Rev Respir Dis 146: 43‐46, 1992.
 363. Mitaka C, Hirata Y, Nagura T, Tsunoda Y, Amaha K. Beneficial effect of atrial natriuretic peptide on pulmonary gas exchange in patients with acute lung injury. Chest 114: 223‐228, 1998.
 364. Miyawaki‐Shimizu K, Predescu D, Shimizu J, Broman M, Predescu S, Malik AB. siRNA‐induced caveolin‐1 knockdown in mice increases lung vascular permeability via the junctional pathway. Am J Physiol 290: L405‐L413, 2006.
 365. Miyoshi J, Takai Y. Molecular perspective on tight‐junction assembly and epithelial polarity. Adv Drug Deliv Rev 57: 815‐855, 2005.
 366. Moldobaeva A, Welsh‐Servinsky LE, Shimoda LA, Stephens RS, Verin AD, Tuder RM, Pearse DB. Role of protein kinase G in barrier‐protective effects of cGMP in human pulmonary artery endothelial cells. Am J Physiol 290: L919‐L930, 2006.
 367. Moncada S. Review. Adventures in vascular biology: A tale of two mediators. Philos Trans R Soc Lond B Biol Sci 361: 735‐759, 2006.
 368. Montuschi P, Collins JV, Ciabattoni G, Lazzeri N, Corradi M, Kharitonov SA, Barnes PJ. Exhaled 8‐isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med 162: 1175‐1177, 2000.
 369. Montuschi P, Nightingale JA, Kharitonov SA, Barnes PJ. Ozone‐induced increase in exhaled 8‐isoprostane in healthy subjects is resistant to inhaled budesonide. Free Radic Biol Med 33: 1403‐1408, 2002.
 370. Morita K, Sasaki H, Furuse M, Tsukita S. Endothelial claudin: Claudin‐5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol 147: 185‐194, 1999.
 371. Morrow JD, Roberts LJ. The isoprostanes: Their role as an index of oxidant stress status in human pulmonary disease. Am J Respir Crit Care Med 166: S25‐S30, 2002.
 372. Moy AB, Blackwell K, Kamath A. Differential effects of histamine and thrombin on endothelial barrier function through actin‐myosin tension. Am J Physiol Heart Circ Physiol 282: H21‐H29, 2002.
 373. Moy AB, Van Engelenhoven J, Bodmer J, Kamath J, Keese C, Giaever I, Shasby S, Shasby DM. Histamine and thrombin modulate endothelial focal adhesion through centripetal and centrifugal forces. J Clin Invest 97: 1020‐1027, 1996.
 374. Mukaida N. Pathophysiological roles of interleukin‐8/CXCL8 in pulmonary diseases. Am J Physiol 284: L566‐L577, 2003.
 375. Muller T, Choidas A, Reichmann E, Ullrich A. Phosphorylation and free pool of beta‐catenin are regulated by tyrosine kinases and tyrosine phosphatases during epithelial cell migration. J Biol Chem 274: 10173‐10183, 1999.
 376. Mullins RD. How WASP‐family proteins and the Arp2/3 complex convert intracellular signals into cytoskeletal structures. Curr Opin Cell Biol 12: 91‐96, 2000.
 377. Mullins RD, Heuser JA, Pollard TD. The interaction of Arp2/3 complex with actin: Nucleation, high affinity pointed end capping, formation of branching networks of filaments. Proc Natl Acad Sci U S A 95: 6181‐6186, 1998.
 378. Munoz‐Chapuli R, Quesada AR, Angel Medina M. Angiogenesis and signal transduction in endothelial cells. Cell Mol Life Sci 61: 2224‐2243, 2004.
 379. Murohara T, Kugiyama K, Ota Y, Doi H, Ogata N, Ohgushi M, Yasue H. Effects of atrial and brain natriuretic peptides on lysophosphatidylcholine‐mediated endothelial dysfunction. J Cardiovasc Pharmacol 34: 870‐878, 1999.
 380. Naidu BV, Woolley SM, Farivar AS, Thomas R, Fraga C, Mulligan MS. Simvastatin ameliorates injury in an experimental model of lung ischemia‐reperfusion. J Thorac Cardiovasc Surg 126: 482‐489, 2003.
 381. Nakagawa M, Fukata M, Yamaga M, Itoh N, Kaibuchi K. Recruitment and activation of Rac1 by the formation of E‐cadherin‐mediated cell‐cell adhesion sites. J Cell Sci 114: 1829‐1838, 2001.
 382. Naruse K, Sai X, Yokoyama N, Sokabe M. Uni‐axial cyclic stretch induces c‐src activation and translocation in human endothelial cells via SA channel activation. FEBS Lett 441: 111‐115, 1998.
 383. Naruse K, Yamada T, Sai XR, Hamaguchi M, Sokabe M. Pp125FAK is required for stretch dependent morphological response of endothelial cells. Oncogene 17: 455‐463, 1998.
 384. Natarajan V, Taher MM, Roehm B, Parinandi NL, Schmid HH, Kiss Z, Garcia JG. Activation of endothelial cell phospholipase D by hydrogen peroxide and fatty acid hydroperoxide. J Biol Chem 268: 930‐937, 1993.
 385. Nawroth R, Poell G, Ranft A, Kloep S, Samulowitz U, Fachinger G, Golding M, Shima DT, Deutsch U, Vestweber D. VE‐PTP and VE‐cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts. EMBO J 21: 4885‐4895, 2002.
 386. Nelson JL, DeMichele SJ, Pacht ER, Wennberg AK. Effect of enteral feeding with eicosapentaenoic acid, gamma‐linolenic acid, and antioxidants on antioxidant status in patients with acute respiratory distress syndrome. JPEN J Parenter Enteral Nutr 27: 98‐104, 2003.
 387. Nguyen L, Holgado‐Madruga M, Maroun C, Fixman ED, Kamikura D, Fournier T, Charest A, Tremblay ML, Wong AJ, Park M. Association of the multisubstrate docking protein Gab1 with the hepatocyte growth factor receptor requires a functional Grb2 binding site involving tyrosine 1356. J Biol Chem 272: 20811‐20819, 1997.
 388. Noll T, Holschermann H, Koprek K, Gunduz D, Haberbosch W, Tillmanns H, Piper HM. ATP reduces macromolecule permeability of endothelial monolayers despite increasing [Ca2+]i. Am J Physiol 276: H1892‐H1901, 1999.
 389. Nonas S, Birukova AA, Fu P, Xing J, Chatchavalvanich S, Bochkov VN, Leitinger N, Garcia JG, Birukov KG. Oxidized phospholipids reduce ventilator‐induced vascular leak and inflammation in vivo. Crit Care 12: R27, 2008.
 390. Nonas SA, Miller I, Kawkitinarong K, Chatchavalvanich S, Gorshkova I, Bochkov VN, Leitinger N, Natarajan V, Garcia JG, Birukov KG. Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury. Am J Respir Crit Care Med 173: 1130‐1138, 2006.
 391. Noren NK, Arthur WT, Burridge K. Cadherin engagement inhibits RhoA via p190RhoGAP. J Biol Chem 278: 13615‐13618, 2003.
 392. Noren NK, Liu BP, Burridge K, Kreft B. p120 catenin regulates the actin cytoskeleton via Rho family GTPases. J Cell Biol 150: 567‐580, 2000.
 393. Noren NK, Niessen CM, Gumbiner BM, Burridge K. Cadherin engagement regulates Rho family GTPases. J Biol Chem 276: 33305‐33308, 2001.
 394. Noritake J, Watanabe T, Sato K, Wang S, Kaibuchi K. IQGAP1: A key regulator of adhesion and migration. J Cell Sci 118: 2085‐2092, 2005.
 395. North RA. Molecular physiology of P2X receptors. Physiol Rev 82: 1013‐1067, 2002.
 396. O'Connor KL, Mercurio AM. Protein kinase A regulates Rac and is required for the growth factor‐stimulated migration of carcinoma cells. J Biol Chem 276: 47895‐47900, 2001.
 397. Ohki Y, Mayuzumi H, Tokuyama K, Yoshizawa Y, Arakawa H, Mochizuki H, Morikawa A. Hepatocyte growth factor treatment improves alveolarization in a newborn murine model of bronchopulmonary dysplasia. Neonatology 95: 332‐338, 2009.
 398. Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin LJ, Nikkho S, Speich R, Hoeper MM, Behr J, Winkler J, Sitbon O, Popov W, Ghofrani HA, Manes A, Kiely DG, Ewert R, Meyer A, Corris PA, Delcroix M, Gomez‐Sanchez M, Siedentop H, Seeger W. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 347: 322‐329, 2002.
 399. Oppermann H, Levinson W, Bishop JM. A cellular protein that associates with the transforming protein of Rous sarcoma virus is also a heat‐shock protein. Proc Natl Acad Sci U S A 78: 1067‐1071, 1981.
 400. Ostermann G, Weber KS, Zernecke A, Schroder A, Weber C. JAM‐1 is a ligand of the beta(2) integrin LFA‐1 involved in transendothelial migration of leukocytes. Nat Immunol 3: 151‐158, 2002.
 401. Owens DW, McLean GW, Wyke AW, Paraskeva C, Parkinson EK, Frame MC, Brunton VG. The catalytic activity of the Src family kinases is required to disrupt cadherin‐dependent cell‐cell contacts. Mol Biol Cell 11: 51‐64, 2000.
 402. Palmeri D, van Zante A, Huang CC, Hemmerich S, Rosen SD. Vascular endothelial junction‐associated molecule, a novel member of the immunoglobulin superfamily, is localized to intercellular boundaries of endothelial cells. J Biol Chem 275: 19139‐19145, 2000.
 403. Panos RJ, Bak PM, Simonet WS, Rubin JS, Smith LJ. Intratracheal instillation of keratinocyte growth factor decreases hyperoxia‐induced mortality in rats. J Clin Invest 96: 2026‐2033, 1995.
 404. Panos RJ, Rubin JS, Csaky KG, Aaronson SA, Mason RJ. Keratinocyte growth factor and hepatocyte growth factor/scatter factor are heparin‐binding growth factors for alveolar type II cells in fibroblast‐conditioned medium. J Clin Invest 92: 969‐977, 1993.
 405. Park GY, Christman JW. Involvement of cyclooxygenase‐2 and prostaglandins in the molecular pathogenesis of inflammatory lung diseases. Am J Physiol 290: L797‐L805, 2006.
 406. Park WY, Goodman RB, Steinberg KP, Ruzinski JT, Radella F, II, Park DR, Pugin J, Skerrett SJ, Hudson LD, Martin TR. Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 164: 1896‐1903, 2001.
 407. Parker JC. Inhibitors of myosin light chain kinase and phosphodiesterase reduce ventilator‐induced lung injury. J Appl Physiol 89: 2241‐2248, 2000.
 408. Parsons JT, Martin KH, Slack JK, Taylor JM, Weed SA. Focal adhesion kinase: A regulator of focal adhesion dynamics and cell movement. Oncogene 19: 5606‐5613, 2000.
 409. Parsons PE, Eisner MD, Thompson BT, Matthay MA, Ancukiewicz M, Bernard GR, Wheeler AP. Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med 33: 1‐6; discussion 230‐232, 2005.
 410. Patterson CE, Lum H, Schaphorst KL, Verin AD, Garcia JG. Regulation of endothelial barrier function by the cAMP‐dependent protein kinase. Endothelium 7: 287‐308, 2000.
 411. Pearse DB, Shimoda LA, Verin AD, Bogatcheva N, Moon C, Ronnett GV, Welsh LE, Becker PM. Effect of cGMP on lung microvascular endothelial barrier dysfunction following hydrogen peroxide. Endothelium 10: 309‐317, 2003.
 412. Pearson JD, Gordon JL. Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides. Nature 281: 384‐386, 1979.
 413. Pedram A, Razandi M, Levin ER. Deciphering vascular endothelial cell growth factor/vascular permeability factor signaling to vascular permeability. Inhibition by atrial natriuretic peptide. J Biol Chem 277: 44385‐44398, 2002.
 414. Peng X, Hassoun PM, Sammani S, McVerry BJ, Burne MJ, Rabb H, Pearse D, Tuder RM, Garcia JG. Protective effects of sphingosine 1‐phosphate in murine endotoxin‐induced inflammatory lung injury. Am J Respir Crit Care Med 169: 1245‐1251, 2004.
 415. Pennathur S, Bergt C, Shao B, Byun J, Kassim SY, Singh P, Green PS, McDonald TO, Brunzell J, Chait A, Oram JF, O'Brien K, Geary RL, Heinecke JW. Human atherosclerotic intima and blood of patients with established coronary artery disease contain high density lipoprotein damaged by reactive nitrogen species. J Biol Chem 279: 42977‐42983, 2004.
 416. Perlman MB, Lo SK, Malik AB. Effect of prostacyclin on pulmonary vascular response to thrombin in awake sheep. J Appl Physiol 60: 546‐553, 1986.
 417. Peters SL, Alewijnse AE. Sphingosine‐1‐phosphate signaling in the cardiovascular system. Curr Ppin Pharmacol 7: 186‐192, 2007.
 418. Petrache I, Birukov K, Zaiman AL, Crow MT, Deng H, Wadgaonkar R, Romer LH, Garcia JG. Caspase‐dependent cleavage of myosin light chain kinase (MLCK) is involved in TNF‐alpha‐mediated bovine pulmonary endothelial cell apoptosis. Faseb J 17: 407‐416, 2003.
 419. Petrache I, Birukova A, Ramirez SI, Garcia JG, Verin AD. The role of the microtubules in tumor necrosis factor‐alpha‐induced endothelial cell permeability. Am J Respir Cell Mol Biol 28: 574‐581, 2003.
 420. Pike LJ. Lipid rafts: Heterogeneity on the high seas. Biochem J 378: 281‐292, 2004.
 421. Pimentel DR, Amin JK, Xiao L, Miller T, Viereck J, Oliver‐Krasinski J, Baliga R, Wang J, Siwik DA, Singh K, Pagano P, Colucci WS, Sawyer DB. Reactive oxygen species mediate amplitude‐dependent hypertrophic and apoptotic responses to mechanical stretch in cardiac myocytes. Circ Res 89: 453‐460, 2001.
 422. Pittet JF, Griffiths MJ, Geiser T, Kaminski N, Dalton SL, Huang X, Brown LA, Gotwals PJ, Koteliansky VE, Matthay MA, Sheppard D. TGF‐beta is a critical mediator of acute lung injury. J Clin Invest 107: 1537‐1544, 2001.
 423. Pizurki L, Zhou Z, Glynos K, Roussos C, Papapetropoulos A. Angiopoietin‐1 inhibits endothelial permeability, neutrophil adherence and IL‐8 production. Br J Pharmacol 139: 329‐336, 2003.
 424. Pollard TD. Actin. Curr Opin Cell Biol 2: 33‐40, 1990.
 425. Pollard TD, Borisy GG. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112: 453‐465, 2003.
 426. Ponzetto C, Bardelli A, Zhen Z, Maina F, dalla Zonca P, Giordano S, Graziani A, Panayotou G, Comoglio PM. A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell 77: 261‐271, 1994.
 427. Potter LR. Domain analysis of human transmembrane guanylyl cyclase receptors: Implications for regulation. Front Biosci 10: 1205‐1220, 2005.
 428. Preston GM, Agre P. Isolation of the cDNA for erythrocyte integral membrane protein of 28 kilodaltons: Member of an ancient channel family. Proc Natl Acad Sci U S A 88: 11110‐11114, 1991.
 429. Price CJ, Brindle NP. Vasodilator‐stimulated phosphoprotein is involved in stress‐fiber and membrane ruffle formation in endothelial cells. Arterioscler Thromb Vasc Biol 20: 2051‐2056, 2000.
 430. Price LS, Hajdo‐Milasinovic A, Zhao J, Zwartkruis FJ, Collard JG, Bos JL. Rap1 regulates E‐cadherin‐mediated cell‐cell adhesion. J Biol Chem 279: 35127‐35132, 2004.
 431. Puddicombe SM, Polosa R, Richter A, Krishna MT, Howarth PH, Holgate ST, Davies DE. Involvement of the epidermal growth factor receptor in epithelial repair in asthma. FASEB J 14: 1362‐1374, 2000.
 432. Pugin J, Dunn I, Jolliet P, Tassaux D, Magnenat JL, Nicod LP, Chevrolet JC. Activation of human macrophages by mechanical ventilation in vitro. Am J Physiol 275: L1040‐L1050, 1998.
 433. Puri A, McGoon MD, Kushwaha SS. Pulmonary arterial hypertension: Current therapeutic strategies. Nat Clin Pract Cardiovasc Med 4: 319‐329, 2007.
 434. Puybasset L, Cluzel P, Chao N, Slutsky AS, Coriat P, Rouby JJ. A computed tomography scan assessment of regional lung volume in acute lung injury. The CT Scan ARDS Study Group. Am J Respir Crit Care Med 158: 1644‐1655, 1998.
 435. Qiao J, Huang F, Lum H. PKA inhibits RhoA activation: A protection mechanism against endothelial barrier dysfunction. Am J Physiol 284: L972‐L980, 2003.
 436. Qiao J, Huang F, Naikawadi RP, Kim KS, Said T, Lum H. Lysophosphatidylcholine impairs endothelial barrier function through the G protein‐coupled receptor GPR4. Am J Physiol 291: L91‐L101, 2006.
 437. Quadri SK, Bhattacharjee M, Parthasarathi K, Tanita T, Bhattacharya J. Endothelial barrier strengthening by activation of focal adhesion kinase. J Biol Chem 278: 13342‐13349, 2003.
 438. Quadri SK, Bhattacharya J. Resealing of endothelial junctions by focal adhesion kinase. Am J Physiol 292: L334‐L342, 2007.
 439. Quesnel C, Marchand‐Adam S, Fabre A, Marchal‐Somme J, Philip I, Lasocki S, Lecon V, Crestani B, Dehoux M. Regulation of hepatocyte growth factor secretion by fibroblasts in patients with acute lung injury. Am J Physiol 294: L334‐L343, 2008.
 440. Quinlan GJ, Lamb NJ, Evans TW, Gutteridge JM. Plasma fatty acid changes and increased lipid peroxidation in patients with adult respiratory distress syndrome. Crit Care Med 24: 241‐246, 1996.
 441. Rana R, Vlahakis NE, Daniels CE, Jaffe AS, Klee GG, Hubmayr RD, Gajic O. B‐type natriuretic peptide in the assessment of acute lung injury and cardiogenic pulmonary edema. Crit Care Med 34: 1941‐1946, 2006.
 442. Rangarajan S, Enserink JM, Kuiperij HB, de Rooij J, Price LS, Schwede F, Bos JL. Cyclic AMP induces integrin‐mediated cell adhesion through Epac and Rap1 upon stimulation of the beta 2‐adrenergic receptor. J Cell Biol 160: 487‐493, 2003.
 443. Ray P. Protection of epithelial cells by keratinocyte growth factor signaling. Proc Am Thorac Soc 2: 221‐225, 2005.
 444. Ray P, Devaux Y, Stolz DB, Yarlagadda M, Watkins SC, Lu Y, Chen L, Yang XF, Ray A. Inducible expression of keratinocyte growth factor (KGF) in mice inhibits lung epithelial cell death induced by hyperoxia. Proc Natl Acad Sci U S A 100: 6098‐6103, 2003.
 445. Reinhard M, Giehl K, Abel K, Haffner C, Jarchau T, Hoppe V, Jockusch BM, Walter U. The proline‐rich focal adhesion and microfilament protein VASP is a ligand for profilins. EMBO J 14: 1583‐1589, 1995.
 446. Ren Y, Li R, Zheng Y, Busch H. Cloning and characterization of GEF‐H1, a microtubule‐associated guanine nucleotide exchange factor for Rac and Rho GTPases. J Biol Chem 273: 34954‐34960, 1998.
 447. Renkin EM, Carter RD, Joyner WL. Mechanism of the sustained action of histamine and bradykinin on transport of large molecules across capillary walls in the dog paw. Microvasc Res 7: 49‐60, 1974.
 448. Rentsendorj O, Mirzapoiazova T, Adyshev D, Servinsky LE, Renne T, Verin AD, Pearse DB. Role of vasodilator‐stimulated phosphoprotein in cGMP‐mediated protection of human pulmonary artery endothelial barrier function. Am J Physiol 294: L686‐L697, 2008.
 449. Reynolds AB. p120‐catenin: Past and present. Biochim Biophys Acta 1773: 2‐7, 2007.
 450. Reynolds AB, Roczniak‐Ferguson A. Emerging roles for p120‐catenin in cell adhesion and cancer. Oncogene 23: 7947‐7956, 2004.
 451. Ricard JD, Dreyfuss D, Saumon G. Ventilator‐induced lung injury. Eur Respir J Suppl 42: 2s‐9s, 2003.
 452. Ridley AJ. Rho family proteins: Coordinating cell responses. Trends Cell Biol 11: 471‐477, 2001.
 453. Riewald M, Petrovan RJ, Donner A, Mueller BM, Ruf W. Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science 296: 1880‐1882, 2002.
 454. Rippe B, Rosengren BI, Carlsson O, Venturoli D. Transendothelial transport: The vesicle controversy. J Vasc Res 39: 375‐390, 2002.
 455. Ritchie RH, Rosenkranz AC, Huynh LP, Stephenson T, Kaye DM, Dusting GJ. Activation of IP prostanoid receptors prevents cardiomyocyte hypertrophy via cAMP‐dependent signaling. Am J Physiol Heart Circ Physiol 287: H1179‐H1185, 2004.
 456. Riva CM, Morganroth ML, Ljungman AG, Schoeneich SO, Marks RM, Todd RF, III, Ward PA, Boxer LA. Iloprost inhibits neutrophil‐induced lung injury and neutrophil adherence to endothelial monolayers. Am J Respir Cell Mol Biol 3: 301‐309, 1990.
 457. Romer LH, Birukov KG, Garcia JG. Focal adhesions: Paradigm for a signaling nexus. Circ Res 98: 606‐616, 2006.
 458. Rosen EM, Goldberg ID. Scatter factor and angiogenesis. Adv Cancer Res 67: 257‐279, 1995.
 459. Rosen H, Goetzl EJ. Sphingosine 1‐phosphate and its receptors: An autocrine and paracrine network. Nat rev 5: 560‐570, 2005.
 460. Roura S, Miravet S, Piedra J, Garcia de Herreros A, Dunach M. Regulation of E‐cadherin/Catenin association by tyrosine phosphorylation. J Biol Chem 274: 36734‐36740, 1999.
 461. Roy AJ, Djerassi I. Effects of platelet transfusions: Plug formation and maintenance of vascular integrity. Proc Soc Exp Biol Med 139: 137‐142, 1972.
 462. Rubin JS, Chan AM, Bottaro DP, Burgess WH, Taylor WG, Cech AC, Hirschfield DW, Wong J, Miki T, Finch PW, Aaronson SA. A broad‐spectrum human lung fibroblast‐derived mitogen is a variant of hepatocyte growth factor. Proc Natl Acad Sci U S A 88: 415‐419, 1991.
 463. Rubin JS, Osada H, Finch PW, Taylor WG, Rudikoff S, Aaronson SA. Purification and characterization of a newly identified growth factor specific for epithelial cells. Proc Natl Acad Sci U S A 86: 802‐806, 1989.
 464. Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P. Binding of GSK3beta to the APC‐beta‐catenin complex and regulation of complex assembly. Science 272: 1023‐1026, 1996.
 465. Russo A, Soh UJ, Paing MM, Arora P, Trejo J. Caveolae are required for protease‐selective signaling by protease‐activated receptor‐1. Proc Natl Acad Sci U S A 106: 6393‐6397, 2009.
 466. Sabath E, Negoro H, Beaudry S, Paniagua M, Angelow S, Shah J, Grammatikakis N, Yu AS, Denker BM. Galpha12 regulates protein interactions within the MDCK cell tight junction and inhibits tight‐junction assembly. J Cell Sci 121: 814‐824, 2008.
 467. Saharinen P, Kerkela K, Ekman N, Marron M, Brindle N, Lee GM, Augustin H, Koh GY, Alitalo K. Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2. J Cell Biol 169: 239‐243, 2005.
 468. Sai X, Naruse K, Sokabe M. Activation of pp60(src) is critical for stretch‐induced orienting response in fibroblasts. J Cell Sci 112: 1365‐1373, 1999.
 469. Sakurai H, Nozaki M, Traber KS, Traber DL. Atrial natriuretic peptide release associated with smoke inhalation and physiological responses to thermal injury in sheep. Burns 31: 737‐743, 2005.
 470. Sanders LC, Matsumura F, Bokoch GM, de Lanerolle P. Inhibition of myosin light chain kinase by p21‐activated kinase [see comments]. Science 283: 2083‐2085, 1999.
 471. Sandoval R, Malik AB, Minshall RD, Kouklis P, Ellis CA, Tiruppathi C. Ca(2+) signalling and PKCalpha activate increased endothelial permeability by disassembly of VE‐cadherin junctions. J Physiol 533: 433‐445, 2001.
 472. Satchell SC, Anderson KL, Mathieson PW. Angiopoietin 1 and vascular endothelial growth factor modulate human glomerular endothelial cell barrier properties. J Am Soc Nephrol 15: 566‐574, 2004.
 473. Sato N, Yamamoto T, Sekine Y, Yumioka T, Junicho A, Fuse H, Matsuda T. Involvement of heat‐shock protein 90 in the interleukin‐6‐mediated signaling pathway through STAT3. Biochem Biophys Res Commun 300: 847‐852, 2003.
 474. Savla U, Waters CM. Barrier function of airway epithelium: Effects of radiation and protection by keratinocyte growth factor. Radiat Res 150: 195‐203, 1998.
 475. Schaeper U, Gehring NH, Fuchs KP, Sachs M, Kempkes B, Birchmeier W. Coupling of Gab1 to c‐Met, Grb2, and Shp2 mediates biological responses. J Cell Biol 149: 1419‐1432, 2000.
 476. Schaller MD. Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim Biophys Acta 1540: 1‐21, 2001.
 477. Schaphorst KL, Chiang E, Jacobs KN, Zaiman A, Natarajan V, Wigley F, Garcia JG. Role of sphingosine‐1 phosphate in the enhancement of endothelial barrier integrity by platelet‐released products. Am J Physiol 285: L258‐L267, 2003.
 478. Schmeck J, Heller A, Groschler A, Recker A, Neuhof H, Urbaschek R, Koch T. Impact of endothelin‐1 in endotoxin‐induced pulmonary vascular reactions. Crit Care Med 28: 2851‐2857, 2000.
 479. Schmidt A, Hall A. Guanine nucleotide exchange factors for Rho GTPases: Turning on the switch. Genes Dev 16: 1587‐1609, 2002.
 480. Schmidt R, Schafer C, Luboeinski T, Lockinger A, Hermle G, Grimminger F, Seeger W, Ghofrani A, Schutte H, Gunther A. Increase in alveolar antioxidant levels in hyperoxic and anoxic ventilated rabbit lungs during ischemia. Free Radic Biol Med 36: 78‐89, 2004.
 481. Schneeberger EE. Structure of intercellular junctions in different segments of the intrapulmonary vasculature. Ann N Y Acad Sci 384: 54‐63, 1982.
 482. Schnyder‐Candrian S, Quesniaux VF, Di Padova F, Maillet I, Noulin N, Couillin I, Moser R, Erard F, Vargaftig BB, Ryffel B, Schnyder B. Dual effects of p38 MAPK on TNF‐dependent bronchoconstriction and TNF‐independent neutrophil recruitment in lipopolysaccharide‐induced acute respiratory distress syndrome. J Immunol 175: 262‐269, 2005.
 483. Schuepbach RA, Feistritzer C, Fernandez JA, Griffin JH, Riewald M. Protection of vascular barrier integrity by activated protein C in murine models depends on protease‐activated receptor‐1. Thromb Haemost 101: 724‐733, 2009.
 484. Schutte H, Lockinger A, Seeger W, Grimminger F. Aerosolized PGE1, PGI2 and nitroprusside protect against vascular leakage in lung ischaemia‐reperfusion. Eur Respir J 18: 15‐22, 2001.
 485. Schwartz MA, Desimone DW. Cell adhesion receptors in mechanotransduction. Curr Opin Cell Biol 20: 551‐556, 2008.
 486. Schwiebert LM, Rice WC, Kudlow BA, Taylor AL, Schwiebert EM. Extracellular ATP signaling and P2X nucleotide receptors in monolayers of primary human vascular endothelial cells. Am J Physiol Cell Physiol 282: C289‐C301, 2002.
 487. Sells MA, Boyd JT, Chernoff J. p21‐activated kinase 1 (Pak1) regulates cell motility in mammalian fibroblasts. J Cell Biol 145: 837‐849, 1999.
 488. Severgnini M, Takahashi S, Tu P, Perides G, Homer RJ, Jhung JW, Bhavsar D, Cochran BH, Simon AR. Inhibition of the Src and Jak kinases protects against lipopolysaccharide‐induced acute lung injury. Am J Respir Crit Care Med 171: 858‐867, 2005.
 489. Shajahan AN, Timblin BK, Sandoval R, Tiruppathi C, Malik AB, Minshall RD. Role of Src‐induced dynamin‐2 phosphorylation in caveolae‐mediated endocytosis in endothelial cells. J Biol Chem 279: 20392‐20400, 2004.
 490. Shanely RA, Zergeroglu MA, Lennon SL, Sugiura T, Yimlamai T, Enns D, Belcastro A, Powers SK. Mechanical ventilation‐induced diaphragmatic atrophy is associated with oxidative injury and increased proteolytic activity. Am J Respir Crit Care Med 166: 1369‐1374, 2002.
 491. Shasby DM, Lind SE, Shasby SS, Goldsmith JC, Hunninghake GW. Reversible oxidant‐induced increases in albumin transfer across cultured endothelium: Alterations in cell shape and calcium homeostasis. Blood 65: 605‐614, 1985.
 492. Shasby DM, Ries DR, Shasby SS, Winter MC. Histamine stimulates phosphorylation of adherens junction proteins and alters their link to vimentin. Am J Physiol 282: L1330‐L1338, 2002.
 493. Shaw SK, Bamba PS, Perkins BN, Luscinskas FW. Real‐time imaging of vascular endothelial‐cadherin during leukocyte transmigration across endothelium. J Immunol 167: 2323‐2330, 2001.
 494. She J, Goolaerts A, Shen J, Bi J, Tong L, Gao L, Song Y, Bai C. KGF‐2 targets alveolar epithelia and capillary endothelia to reduce high altitude pulmonary edema in rats. J Cell Mol Med doi: 10.1111/j.1582‐4934.2012.01588.x., 2012.
 495. Shen L, Turner JR. Actin depolymerization disrupts tight junctions via caveolae‐mediated endocytosis. Mol Biol Cell 16: 3919‐3936, 2005.
 496. Shi S, Garcia JG, Roy S, Parinandi NL, Natarajan V. Involvement of c‐Src in diperoxovanadate‐induced endothelial cell barrier dysfunction. Am J Physiol 279: L441‐L451, 2000.
 497. Shigemura N, Sawa Y, Mizuno S, Ono M, Ohta M, Nakamura T, Kaneda Y, Matsuda H. Amelioration of pulmonary emphysema by in vivo gene transfection with hepatocyte growth factor in rats. Circulation 111: 1407‐1414, 2005.
 498. Shikata Y, Rios A, Kawkitinarong K, DePaola N, Garcia JG, Birukov KG. Differential effects of shear stress and cyclic stretch on focal adhesion remodeling, site‐specific FAK phosphorylation, and small GTPases in human lung endothelial cells. Exp Cell Res 304: 40‐49, 2005.
 499. Siflinger‐Birnboim A, Del Vecchio PJ, Cooper JA, Blumenstock FA, Shepard JM, Malik AB. Molecular sieving characteristics of the cultured endothelial monolayer. J Cell Physiol 132: 111‐117, 1987.
 500. Siflinger‐Birnboim A, Johnson A. Protein kinase C modulates pulmonary endothelial permeability: A paradigm for acute lung injury. Am J Physiol 284: L435‐L451, 2003.
 501. Siflinger‐Birnboim A, Lum H, Del Vecchio PJ, Malik AB. Involvement of Ca2+ in the H2O2‐induced increase in endothelial permeability. Am J Physiol 270: L973‐L978, 1996.
 502. Singleton PA, Chatchavalvanich S, Fu P, Xing J, Birukova AA, Fortune JA, Klibanov AM, Garcia JG, Birukov KG. Akt‐mediated transactivation of the S1P1 receptor in caveolin‐enriched microdomains regulates endothelial barrier enhancement by oxidized phospholipids. Circ Res 104: 978‐986, 2009.
 503. Singleton PA, Dudek SM, Chiang ET, Garcia JG. Regulation of sphingosine 1‐phosphate‐induced endothelial cytoskeletal rearrangement and barrier enhancement by S1P1 receptor, PI3 kinase, Tiam1/Rac1, and alpha‐actinin. Faseb J 19: 1646‐1656, 2005.
 504. Singleton PA, Dudek SM, Ma SF, Garcia JG. Transactivation of sphingosine 1‐phosphate receptors is essential for vascular barrier regulation. Novel role for hyaluronan and CD44 receptor family. J Biol Chem 281: 34381‐34393, 2006.
 505. Singleton PA, Moreno‐Vinasco L, Sammani S, Wanderling SL, Moss J, Garcia JG. Attenuation of vascular permeability by methylnaltrexone: Role of mOP‐R and S1P3 transactivation. Am J Respir Cell Mol Biol 37: 222‐231, 2007.
 506. Singleton PA, Salgia R, Moreno‐Vinasco L, Moitra J, Sammani S, Mirzapoiazova T, Garcia JG. CD44 regulates hepatocyte growth factor‐mediated vascular integrity. Role of c‐Met, Tiam1/Rac1, dynamin 2, and cortactin. J Biol Chem 282: 30643‐30657, 2007.
 507. Smith PG, Garcia R, Kogerman L. Mechanical strain increases protein tyrosine phosphorylation in airway smooth muscle cells. Exp Cell Res 239: 353‐360, 1998.
 508. Smith PG, Tokui T, Ikebe M. Mechanical strain increases contractile enzyme activity in cultured airway smooth muscle cells. Am J Physiol 268: L999‐L1005, 1995.
 509. Sohara Y. Reexpansion pulmonary edema. Ann Thorac Cardiovasc Surg 14: 205‐209, 2008.
 510. Stan RV. Structure and function of endothelial caveolae. Microsc Res Tech 57: 350‐364, 2002.
 511. Stephens LR, Eguinoa A, Erdjument‐Bromage H, Lui M, Cooke F, Coadwell J, Smrcka AS, Thelen M, Cadwallader K, Tempst P, Hawkins PT. The G beta gamma sensitivity of a PI3K is dependent upon a tightly associated adaptor, p101. Cell 89: 105‐114, 1997.
 512. Stern JB, Fierobe L, Paugam C, Rolland C, Dehoux M, Petiet A, Dombret MC, Mantz J, Aubier M, Crestani B. Keratinocyte growth factor and hepatocyte growth factor in bronchoalveolar lavage fluid in acute respiratory distress syndrome patients. Crit Care Med 28: 2326‐2333, 2000.
 513. Stern JB, Jaffre S, Dehoux M, Crestani B. [Keratinocyte growth factor and Hepatocyte growth factor: Their roles in alveolar epithelial repair]. Rev Mal Respir 20: 896‐903, 2003.
 514. Sturn DH, Kaneider NC, Feistritzer C, Djanani A, Fukudome K, Wiedermann CJ. Expression and function of the endothelial protein C receptor in human neutrophils. Blood 102: 1499‐1505, 2003.
 515. Sugahara K, Iyama K, Kuroda MJ, Sano K. Double intratracheal instillation of keratinocyte growth factor prevents bleomycin‐induced lung fibrosis in rats. J Pathol 186: 90‐98, 1998.
 516. Sumi T, Matsumoto K, Takai Y, Nakamura T. Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho‐ and Cdc42‐activated LIM‐kinase 2. J Cell Biol 147: 1519‐1532, 1999.
 517. Sun X, Shikata Y, Wang L, Ohmori K, Watanabe N, Wada J, Shikata K, Birukov KG, Makino H, Jacobson JR, Dudek SM, Garcia JG. Enhanced interaction between focal adhesion and adherens junction proteins: Involvement in sphingosine 1‐phosphate‐induced endothelial barrier enhancement. Microvasc Res 77: 304‐313, 2009.
 518. Sun Y, Hu G, Zhang X, Minshall RD. Phosphorylation of caveolin‐1 regulates oxidant‐induced pulmonary vascular permeability via paracellular and transcellular pathways. Circ Res 105: 676‐685, 615 p following 685, 2009.
 519. Sutherland C, Leighton IA, Cohen P. Inactivation of glycogen synthase kinase‐3 beta by phosphorylation: New kinase connections in insulin and growth‐factor signalling. Biochem J 296(Pt 1): 15‐19, 1993.
 520. Svitkina TM, Borisy GG. Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia. J Cell Biol 145: 1009‐1026, 1999.
 521. Takai Y, Nakanishi H. Nectin and afadin: Novel organizers of intercellular junctions. J Cell Sci 116: 17‐27, 2003.
 522. Takeda H, Komori K, Nishikimi N, Nimura Y, Sokabe M, Naruse K. Bi‐phasic activation of eNOS in response to uni‐axial cyclic stretch is mediated by differential mechanisms in BAECs. Life Sci 79: 233‐239, 2006.
 523. Takeoka M, Ward WF, Pollack H, Kamp DW, Panos RJ. KGF facilitates repair of radiation‐induced DNA damage in alveolar epithelial cells. Am J Physiol 272: L1174‐L1180, 1997.
 524. Tanaka N, Kawasaki K, Nejime N, Kubota Y, Nakamura K, Kunitomo M, Takahashi K, Hashimoto M, Shinozuka K. P2Y receptor‐mediated Ca(2+) signaling increases human vascular endothelial cell permeability. J Pharmacol Sci 95: 174‐180, 2004.
 525. Tanaka N, Nejime N, Kagota S, Kubota Y, Yudo K, Nakamura K, Kunitomo M, Takahashi K, Hashimoto M, Shinozuka K. ATP participates in the regulation of microvessel permeability. J Pharm Pharmacol 58: 481‐487, 2006.
 526. Tani M, Ito M, Igarashi Y. Ceramide/sphingosine/sphingosine 1‐phosphate metabolism on the cell surface and in the extracellular space. Cell Signal 19: 229‐237, 2007.
 527. Tapon N, Hall A. Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton. Curr Opin Cell Biol 9: 86‐92, 1997.
 528. Tar K, Birukova AA, Csortos C, Bako E, Garcia JG, Verin AD. Phosphatase 2A is involved in endothelial cell microtubule remodeling and barrier regulation. J Cell Biochem 92: 534‐546, 2004.
 529. Tasaka S, Koh H, Yamada W, Shimizu M, Ogawa Y, Hasegawa N, Yamaguchi K, Ishii Y, Richer SE, Doerschuk CM, Ishizaka A. Attenuation of endotoxin‐induced acute lung injury by the Rho‐associated kinase inhibitor, Y‐27632. Am J Respir Cell Mol Biol 32: 504‐510, 2005.
 530. Tauseef M, Kini V, Knezevic N, Brannan M, Ramchandaran R, Fyrst H, Saba J, Vogel SM, Malik AB, Mehta D. Activation of sphingosine kinase‐1 reverses the increase in lung vascular permeability through sphingosine‐1‐phosphate receptor signaling in endothelial cells. Circ Res 103: 1164‐1172, 2008.
 531. Taylor FB, Jr, Chang A, Esmon CT, D'Angelo A, Vigano‐D'Angelo S, Blick KE. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 79: 918‐925, 1987.
 532. Thomas SM, Brugge JS. Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol 13: 513‐609, 1997.
 533. Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM, Yancopoulos GD. Angiopoietin‐1 protects the adult vasculature against plasma leakage. Nat Med 6: 460‐463, 2000.
 534. Thurston G, Suri C, Smith K, McClain J, Sato TN, Yancopoulos GD, McDonald DM. Leakage‐resistant blood vessels in mice transgenically overexpressing angiopoietin‐1. Science 286: 2511‐2514, 1999.
 535. Tinsley JH, Ustinova EE, Xu W, Yuan SY. Src‐dependent, neutrophil‐mediated vascular hyperpermeability and beta‐catenin modification. Am J Physiol Cell Physiol 283: C1745‐C1751, 2002.
 536. Tiruppathi C, Minshall RD, Paria BC, Vogel SM, Malik AB. Role of Ca2+ signaling in the regulation of endothelial permeability. Vascul Pharmacol 39: 173‐185, 2002.
 537. Tiruppathi C, Naqvi T, Sandoval R, Mehta D, Malik AB. Synergistic effects of tumor necrosis factor‐alpha and thrombin in increasing endothelial permeability. Am J Physiol 281: L958‐L968, 2001.
 538. Tiruppathi C, Song W, Bergenfeldt M, Sass P, Malik AB. Gp60 activation mediates albumin transcytosis in endothelial cells by tyrosine kinase‐dependent pathway. J Biol Chem 272: 25968‐25975, 1997.
 539. Togbe D, Schnyder‐Candrian S, Schnyder B, Doz E, Noulin N, Janot L, Secher T, Gasse P, Lima C, Coelho FR, Vasseur V, Erard F, Ryffel B, Couillin I, Moser R. Toll‐like receptor and tumour necrosis factor dependent endotoxin‐induced acute lung injury. Int J Exp Pathol 88: 387‐391, 2007.
 540. Tokuyama K, Nishimura H, Iizuka K, Kato M, Arakawa H, Saga R, Mochizuki H, Morikawa A. Effects of Y‐27632, a Rho/Rho kinase inhibitor, on leukotriene D(4)‐ and histamine‐induced airflow obstruction and airway microvascular leakage in guinea pigs in vivo. Pharmacology 64: 189‐195, 2002.
 541. Tomita N, Morishita R, Higaki J, Ogihara T. Novel molecular therapeutic approach to cardiovascular disease based on hepatocyte growth factor. J Atheroscler Thromb 7: 1‐7, 2000.
 542. Toole BP. Hyaluronan: From extracellular glue to pericellular cue. Nat Rev Cancer 4: 528‐539, 2004.
 543. Troyanovsky B, Alvarez DF, King JA, Schaphorst KL. Thrombin enhances the barrier function of rat microvascular endothelium in a PAR‐1‐dependent manner. Am J Physiol 294: L266‐L275, 2008.
 544. Tuma PL, Hubbard AL. Transcytosis: Crossing cellular barriers. Physiol Rev 83: 871‐932, 2003.
 545. Turner CE. Paxillin and focal adhesion signalling. Nat Cell Biol 2: E231‐E236, 2000.
 546. Turner CE. Paxillin interactions. J Cell Sci 113(Pt 23): 4139‐4140, 2000.
 547. Turner CE, West KA, Brown MC. Paxillin‐ARF GAP signaling and the cytoskeleton. Curr Opin Cell Biol 13: 593‐599, 2001.
 548. Tzima E, Del Pozo MA, Kiosses WB, Mohamed SA, Li S, Chien S, Schwartz MA. Activation of Rac1 by shear stress in endothelial cells mediates both cytoskeletal reorganization and effects on gene expression. EMBO J 21: 6791‐6800, 2002.
 549. Ueda S, Nishio K, Akai Y, Fukushima H, Ueyama T, Kawai Y, Masui K, Yoshioka A, Okuchi K. Prognostic value of increased plasma levels of brain natriuretic peptide in patients with septic shock. Shock 26: 134‐139, 2006.
 550. Ueno Y, Koike H, Annoh S, Nishio S. Anti‐inflammatory effects of beraprost sodium, a stable analogue of PGI2, and its mechanisms. Prostaglandins 53: 279‐289, 1997.
 551. Uhlig S, Goggel R, Engel S. Mechanisms of platelet‐activating factor (PAF)‐mediated responses in the lung. Pharmacol Rep 57(Suppl): 206‐221, 2005.
 552. Ukropec JA, Hollinger MK, Salva SM, Woolkalis MJ. SHP2 association with VE‐cadherin complexes in human endothelial cells is regulated by thrombin. J Biol Chem 275: 5983‐5986, 2000.
 553. Ukropec JA, Hollinger MK, Woolkalis MJ. Regulation of VE‐cadherin linkage to the cytoskeleton in endothelial cells exposed to fluid shear stress. Exp Cell Res 273: 240‐247, 2002.
 554. Ulich TR, Yi ES, Longmuir K, Yin S, Biltz R, Morris CF, Housley RM, Pierce GF. Keratinocyte growth factor is a growth factor for type II pneumocytes in vivo. J Clin Invest 93: 1298‐1306, 1994.
 555. Uruno T, Liu J, Zhang P, Fan Y, Egile C, Li R, Mueller SC, Zhan X. Activation of Arp2/3 complex‐mediated actin polymerization by cortactin. Nat Cell Biol 3: 259‐266, 2001.
 556. Usatyuk PV, Fomin VP, Shi S, Garcia JG, Schaphorst K, Natarajan V. Role of Ca2+ in diperoxovanadate‐induced cytoskeletal remodeling and endothelial cell barrier function. Am J Physiol 285: L1006‐L1017, 2003.
 557. Usatyuk PV, Natarajan V. Role of mitogen‐activated protein kinases in 4‐hydroxy‐2‐nonenal‐induced actin remodeling and barrier function in endothelial cells. J Biol Chem 279: 11789‐11797, 2004.
 558. Usatyuk PV, Vepa S, Watkins T, He D, Parinandi NL, Natarajan V. Redox regulation of reactive oxygen species‐induced p38 MAP kinase activation and barrier dysfunction in lung microvascular endothelial cells. Antioxid Redox Signal 5: 723‐730, 2003.
 559. van Buul JD, Anthony EC, Fernandez‐Borja M, Burridge K, Hordijk PL. Proline‐rich tyrosine kinase 2 (Pyk2) mediates vascular endothelial‐cadherin‐based cell‐cell adhesion by regulating beta‐catenin tyrosine phosphorylation. J Biol Chem 280: 21129‐21136, 2005.
 560. Van Lenten BJ, Wagner AC, Navab M, Anantharamaiah GM, Hui EK, Nayak DP, Fogelman AM. D‐4F, an apolipoprotein A‐I mimetic peptide, inhibits the inflammatory response induced by influenza A infection of human type II pneumocytes. Circulation 110: 3252‐3258, 2004.
 561. van Nieuw Amerongen GP, Draijer R, Vermeer MA, van Hinsbergh VW. Transient and prolonged increase in endothelial permeability induced by histamine and thrombin: Role of protein kinases, calcium, and RhoA. Circ Res 83: 1115‐1123, 1998.
 562. van Nieuw Amerongen GP, Natarajan K, Yin G, Hoefen RJ, Osawa M, Haendeler J, Ridley AJ, Fujiwara K, van Hinsbergh VW, Berk BC. GIT1 mediates thrombin signaling in endothelial cells: Role in turnover of RhoA‐type focal adhesions. Circ Res 94: 1041‐1049, 2004.
 563. van Nieuw Amerongen GP, van Delft S, Vermeer MA, Collard JG, van Hinsbergh VW. Activation of RhoA by thrombin in endothelial hyperpermeability: Role of Rho kinase and protein tyrosine kinases. Circ Res 87: 335‐340, 2000.
 564. van Nieuw Amerongen GP, Vermeer MA, Negre‐Aminou P, Lankelma J, Emeis JJ, van Hinsbergh VW. Simvastatin improves disturbed endothelial barrier function. Circulation 102: 2803‐2809, 2000.
 565. Vandenbroucke E, Mehta D, Minshall R, Malik AB. Regulation of endothelial junctional permeability. Ann N Y Acad Sci 1123: 134‐145, 2008.
 566. Varani J, Fligiel SE, Till GO, Kunkel RG, Ryan US, Ward PA. Pulmonary endothelial cell killing by human neutrophils. Possible involvement of hydroxyl radical. Lab Invest 53: 656‐663, 1985.
 567. Venkataraman K, Thangada S, Michaud J, Oo ML, Ai Y, Lee YM, Wu M, Parikh NS, Khan F, Proia RL, Hla T. Extracellular export of sphingosine kinase‐1a contributes to the vascular S1P gradient. Biochem J 397: 461‐471, 2006.
 568. Verghese GM, McCormick‐Shannon K, Mason RJ, Matthay MA. Hepatocyte growth factor and keratinocyte growth factor in the pulmonary edema fluid of patients with acute lung injury. Biologic and clinical significance. Am J Respir Crit Care Med 158: 386‐394, 1998.
 569. Verin AD, Birukova A, Wang P, Liu F, Becker P, Birukov K, Garcia JG. Microtubule disassembly increases endothelial cell barrier dysfunction: Role of MLC phosphorylation. Am J Physiol 281: L565‐L574, 2001.
 570. Verin AD, Gilbert‐McClain LI, Patterson CE, Garcia JG. Biochemical regulation of the nonmuscle myosin light chain kinase isoform in bovine endothelium. Am J Respir Cell Mol Biol 19: 767‐776, 1998.
 571. Verkman AS. Role of aquaporin water channels in kidney and lung. Am J Med Sci 316: 310‐320, 1998.
 572. Vlahakis NE, Schroeder MA, Limper AH, Hubmayr RD. Stretch induces cytokine release by alveolar epithelial cells in vitro. Am J Physiol 277: L167‐L173, 1999.
 573. von Lintig FC, Pilz RB, Boss GR. Quantitative determination of Rap 1 activation in cyclic nucleotide‐treated HL‐60 leukemic cells: Lack of Rap 1 activation in variant cells. Oncogene 19: 4029‐4034, 2000.
 574. Vouret‐Craviari V, Boquet P, Pouyssegur J, Van Obberghen‐Schilling E. Regulation of the actin cytoskeleton by thrombin in human endothelial cells: Role of Rho proteins in endothelial barrier function. Mol Biol Cell 9: 2639‐2653, 1998.
 575. Vouret‐Craviari V, Bourcier C, Boulter E, van Obberghen‐Schilling E. Distinct signals via Rho GTPases and Src drive shape changes by thrombin and sphingosine‐1‐phosphate in endothelial cells. J Cell Sci 115: 2475‐2484, 2002.
 576. Wada H, Sakakura M, Kushiya F, Nisikawa M, Onishi K, Nakatani K, Shiku H, Nobori T. Thrombomodulin accelerates activated protein C production and inhibits thrombin generation in the plasma of disseminated intravascular coagulation patients. Blood Coagul Fibrinolysis 16: 17‐24, 2005.
 577. Wade RH, Hyman AA. Microtubule structure and dynamics. Curr Opin Cell Biol 9: 12‐17, 1997.
 578. Wainwright MS, Rossi J, Schavocky J, Crawford S, Steinhorn D, Velentza AV, Zasadzki M, Shirinsky V, Jia Y, Haiech J, Van Eldik LJ, Watterson DM. Protein kinase involved in lung injury susceptibility: Evidence from enzyme isoform genetic knockout and in vivo inhibitor treatment. Proc Natl Acad Sci U S A 100: 6233‐6238, 2003.
 579. Wakabayashi G, Ueda M, Aikawa N, Naruse M, Abe O. Release of ANP and its physiological role in pulmonary injury due to HCl. Am J Physiol 258: R690‐R696, 1990.
 580. Wang DS, Proffit D, Tsao PS. Mechanotransduction of endothelial oxidative stress induced by cyclic strain. Endothelium 8: 283‐291, 2001.
 581. Wang G, Slepushkin VA, Bodner M, Zabner J, van Es HH, Thomas P, Jolly DJ, Davidson BL, McCray PB, Jr. Keratinocyte growth factor induced epithelial proliferation facilitates retroviral‐mediated gene transfer to distal lung epithelia in vivo. J Gene Med 1: 22‐30, 1999.
 582. Wang JG, Miyazu M, Xiang P, Li SN, Sokabe M, Naruse K. Stretch‐induced cell proliferation is mediated by FAK‐MAPK pathway. Life Sci 76: 2817‐2825, 2005.
 583. Wang L, Karlsson L, Moses S, Hultgardh‐Nilsson A, Andersson M, Borna C, Gudbjartsson T, Jern S, Erlinge D. P2 receptor expression profiles in human vascular smooth muscle and endothelial cells. J Cardiovasc Pharmacol 40: 841‐853, 2002.
 584. Ware LB, Matthay MA. Clinical practice. Acute pulmonary edema. N Engl J Med 353: 2788‐2796, 2005.
 585. Watanabe M, Ebina M, Orson FM, Nakamura A, Kubota K, Koinuma D, Akiyama K, Maemondo M, Okouchi S, Tahara M, Matsumoto K, Nakamura T, Nukiwa T. Hepatocyte growth factor gene transfer to alveolar septa for effective suppression of lung fibrosis. Mol Ther 12: 58‐67, 2005.
 586. Watanabe N, Madaule P, Reid T, Ishizaki T, Watanabe G, Kakizuka A, Saito Y, Nakao K, Jockusch BM, Narumiya S. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. EMBO J 16: 3044‐3056, 1997.
 587. Waters CM. Reactive oxygen species in mechanotransduction. Am J Physiol 287: L484‐L485, 2004.
 588. Waters CM, Savla U. Keratinocyte growth factor accelerates wound closure in airway epithelium during cyclic mechanical strain. J Cell Physiol 181: 424‐432, 1999.
 589. Waters CM, Savla U, Panos RJ. KGF prevents hydrogen peroxide‐induced increases in airway epithelial cell permeability. Am J Physiol 272: L681‐L689, 1997.
 590. Webb DJ, Parsons JT, Horwitz AF. Adhesion assembly, disassembly and turnover in migrating cells – over and over and over again. Nat Cell Biol 4: E97‐E100, 2002.
 591. Weed SA, Parsons JT. Cortactin: Coupling membrane dynamics to cortical actin assembly. Oncogene 20: 6418‐6434, 2001.
 592. Weis S, Cui J, Barnes L, Cheresh D. Endothelial barrier disruption by VEGF‐mediated Src activity potentiates tumor cell extravasation and metastasis. J Cell Biol 167: 223‐229, 2004.
 593. Werner S. Keratinocyte growth factor: A unique player in epithelial repair processes. Cytokine Growth Factor Rev 9: 153‐165, 1998.
 594. West KA, Zhang H, Brown MC, Nikolopoulos SN, Riedy MC, Horwitz AF, Turner CE. The LD4 motif of paxillin regulates cell spreading and motility through an interaction with paxillin kinase linker (PKL). J Cell Biol 154: 161‐176, 2001.
 595. Westendorp RG, Draijer R, Meinders AE, van Hinsbergh VW. Cyclic‐GMP‐mediated decrease in permeability of human umbilical and pulmonary artery endothelial cell monolayers. J Vasc Res 31: 42‐51, 1994.
 596. Wheelock MJ, Johnson KR. Cadherin‐mediated cellular signaling. Curr Opin Cell Biol 15: 509‐514, 2003.
 597. Whitson PA, Huls MH, Sams CF. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells. J Cell Physiol 146: 43‐51, 1991.
 598. Witzenbichler B, Westermann D, Knueppel S, Schultheiss HP, Tschope C. Protective role of angiopoietin‐1 in endotoxic shock. Circulation 111: 97‐105, 2005.
 599. Wojciak‐Stothard B, Ridley AJ. Rho GTPases and the regulation of endothelial permeability. Vascul Pharmacol 39: 187‐199, 2002.
 600. Wood LG, Gibson PG, Garg ML. Biomarkers of lipid peroxidation, airway inflammation and asthma. Eur Respir J 21: 177‐186, 2003.
 601. Wu L, Zaborina O, Zaborin A, Chang EB, Musch M, Holbrook C, Shapiro J, Turner JR, Wu G, Lee KY, Alverdy JC. High‐molecular‐weight polyethylene glycol prevents lethal sepsis due to intestinal Pseudomonas aeruginosa. Gastroenterology 126: 488‐498, 2004.
 602. Wu MH, Guo M, Yuan SY, Granger HJ. Focal adhesion kinase mediates porcine venular hyperpermeability elicited by vascular endothelial growth factor. J Physiol 552: 691‐699, 2003.
 603. Xia YP, Zhao Y, Marcus J, Jimenez PA, Ruben SM, Moore PA, Khan F, Mustoe TA. Effects of keratinocyte growth factor‐2 (KGF‐2) on wound healing in an ischaemia‐impaired rabbit ear model and on scar formation. J Pathol 188: 431‐438, 1999.
 604. Xu X, McCormick‐Shannon K, Voelker DR, Mason RJ. KGF increases SP‐A and SP‐D mRNA levels and secretion in cultured rat alveolar type II cells. Am J Respir Cell Mol Biol 18: 168‐178, 1998.
 605. Yamada S, Pokutta S, Drees F, Weis WI, Nelson WJ. Deconstructing the cadherin‐catenin‐actin complex. Cell 123: 889‐901, 2005.
 606. Yamamoto K, Korenaga R, Kamiya A, Qi Z, Sokabe M, Ando J. P2X(4) receptors mediate ATP‐induced calcium influx in human vascular endothelial cells. Am J Physiol Heart Circ Physiol 279: H285‐H292, 2000.
 607. Yamanaka K, Saluja AK, Brown GE, Yamaguchi Y, Hofbauer B, Steer ML. Protective effects of prostaglandin E1 on acute lung injury of caerulein‐induced acute pancreatitis in rats. Am J Physiol 272: G23‐G30, 1997.
 608. Yan SB, Helterbrand JD, Hartman DL, Wright TJ, Bernard GR. Low levels of protein C are associated with poor outcome in severe sepsis. Chest 120: 915‐922, 2001.
 609. Yang L, Yatomi Y, Miura Y, Satoh K, Ozaki Y. Metabolism and functional effects of sphingolipids in blood cells. Br J Haematol 107: 282‐293, 1999.
 610. Yang S, Cheek DJ, Westfall DP, Buxton IL. Purinergic axis in cardiac blood vessels. Agonist‐mediated release of ATP from cardiac endothelial cells. Circ Res 74: 401‐407, 1994.
 611. Yano T, Mason RJ, Pan T, Deterding RR, Nielsen LD, Shannon JM. KGF regulates pulmonary epithelial proliferation and surfactant protein gene expression in adult rat lung. Am J Physiol 279: L1146‐L1158, 2000.
 612. Yatomi Y, Ruan F, Hakomori S, Igarashi Y. Sphingosine‐1‐phosphate: A platelet‐activating sphingolipid released from agonist‐stimulated human platelets. Blood 86: 193‐202, 1995.
 613. Yi ES, Williams ST, Lee H, Malicki DM, Chin EM, Yin S, Tarpley J, Ulich TR. Keratinocyte growth factor ameliorates radiation‐ and bleomycin‐induced lung injury and mortality. Am J Pathol 149: 1963‐1970, 1996.
 614. Yuan SY. Protein kinase signaling in the modulation of microvascular permeability. Vascul Pharmacol 39: 213‐223, 2002.
 615. Yuan Y, Huang Q, Wu HM. Myosin light chain phosphorylation: Modulation of basal and agonist‐stimulated venular permeability. Am J Physiol 272: H1437‐H1443, 1997.
 616. Zandy NL, Pendergast AM. Abl tyrosine kinases modulate cadherin‐dependent adhesion upstream and downstream of Rho family GTPases. Cell Cycle 7: 444‐448, 2008.
 617. Zenke FT, Krendel M, DerMardirossian C, King CC, Bohl BP, Bokoch GM. p21‐activated kinase 1 phosphorylates and regulates 14‐3‐3 binding to GEF‐H1, a microtubule‐localized Rho exchange factor. J Biol Chem 279: 18392‐18400, 2004.
 618. Zhang B, Peng F, Wu D, Ingram AJ, Gao B, Krepinsky JC. Caveolin‐1 phosphorylation is required for stretch‐induced EGFR and Akt activation in mesangial cells. Cell Signal 19: 1690‐1700, 2007.
 619. Zhang D, Wang Z, Jin N, Li L, Rhoades RA, Yancey KW, Swartz DR. Microtubule disruption modulates the Rho‐kinase pathway in vascular smooth muscle. J Muscle Res Cell Motil 22: 193‐200, 2001.
 620. Zhang L, Himi T, Morita I, Murota S. Hepatocyte growth factor protects cultured rat cerebellar granule neurons from apoptosis via the phosphatidylinositol‐3 kinase/Akt pathway. J Neurosci Res 59: 489‐496, 2000.
 621. Zhang ZG, Zhang L, Croll SD, Chopp M. Angiopoietin‐1 reduces cerebral blood vessel leakage and ischemic lesion volume after focal cerebral embolic ischemia in mice. Neuroscience 113: 683‐687, 2002.
 622. Zhao J, Singleton PA, Brown ME, Dudek SM, Garcia JG. Phosphotyrosine protein dynamics in cell membrane rafts of sphingosine‐1‐phosphate‐stimulated human endothelium: Role in barrier enhancement. Cell Signal 21: 1945‐1960, 2009.
 623. Zhao ZS, Manser E, Loo TH, Lim L. Coupling of PAK‐interacting exchange factor PIX to GIT1 promotes focal complex disassembly. Mol Cell Biol 20: 6354‐6363, 2000.
 624. Zheng Y. Dbl family guanine nucleotide exchange factors. Trends Biochem Sci 26: 724‐732, 2001.

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Konstantin G. Birukov, Noureddine Zebda, Anna A. Birukova. Barrier Enhancing Signals in Pulmonary Edema. Compr Physiol 2013, 3: 429-484. doi: 10.1002/cphy.c100066