Comprehensive Physiology Wiley Online Library

The Pulmonary Microcirculation

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Lung Blood Flow
2 The Lung Microvascular Bed
3 Microvascular Liquid Transport
3.1 The Starling forces
3.2 The microvascular barrier
4 Leukocyte Kinetics
4.1 The marginated pool of leukocytes
4.2 Localization and regulation of the marginated pool
4.3 Mechanism of leukocyte margination
4.4 Leukocyte sequestration
4.5 Interaction of leukocytes with platelets
4.6 Interaction of ECs with leukocytes and platelets
4.7 Leukocyte emigration
5 Gap Junctions
5.1 Compatibility of vascular connexins
5.2 Heterogeneity of gap junction composition
5.3 Connexins and vascular tone
5.4 Role of connexins in vessel inflammation and atherosclerosis
6 Conclusion
Figure 1. Figure 1.

Sequential ratiometric images are enlarged views of a single wall of each of two capillaries loaded with fura 2. A. In frame I endothelial cells are outlined and top and bottom arrows are separated by 47μm. Frames were imaged 10s apart. Note, progressive increase of Ca2+ in pacemaker (bottom arrow) generates a Ca2+ wave up the wall. The wave starts receding in frame #6. B. This capillary was treated with the gap junction inhibitor, heptanol (3mM). Note absence of Ca2+ wave, although the pacememaker (arrow) generates increase (frames #1–5) and decrease (frames #6–8) of local Ca2+

adapted from ). (See page 19 in colour section at the back of the book
Figure 2. Figure 2.

Influence of respiratory movements on pulmonary leukocyte kinetics. Graphs depict pulmonary arteriovenous difference in leukocyte concentration during Valsalva (left) and Muller (right) maneuver. Two patients were removed from original Valsalva data by Bierman et al. , one because of very high leukocyte counts due to leukemia, another because of incomplete sampling. Muller maneuver was only performed in 2 patients. *p < 0.05 Wilcoxon matched pairs test.

Figure 3. Figure 3.

Size‐dependence of leukocyte margination. Graph based on original data by Doerschuk et al. and Wiggs et al. . Extraction (mean ± SEM) refers to first passage of cells or microspheres through lungs relative to passage of red blood cells (given as zero extraction). Diameters (given as range) were calculated assuming that cells were spherical. Sigmoidal regression calculated by 4 parameter logistic curve fit.

Figure 4. Figure 4.

Total cell number of the circulating and pulmonary marginated pool in rabbits. Original data on total leukocytes was determined by intravital microscopy, data on PMN is from morphological studies . Data are means ± SEM. a, arterioles; v. venules.

Figure 5. Figure 5.

Vertical gradients of PMN retention and blood flow in the lung. 1 represents top, 6 bottom level of the lung. Percent of PMN retention in lungs of supine mongrel dogs is given in open circles, in supine rabbit lungs in open squares. In rabbits in left lateral position, regional blood flow (closed triangles) was determined by radioactive microspheres and PMN concentration (open triangles) by myeloperoxidase (MPO) assay .

Figure 6. Figure 6.

Leukocyte/endothelial interaction in the ventilated rabbit lung. Images were taken during ventilation with an inspiratory pressure of 8 (A) or 12 (B) mmHg. In the center of the images is a pulmonary arteriole, surrounded by several darker alveoli. Autologous leukocytes were labeled in vivo by rhodamine 6G. Arrowheads mark leukocytes firmly adherent to the vascular wall. Leukocyte accumulation in the terminal arteriolar branches at elevated inspiratory pressure is clearly visible.

Figure 7. Figure 7.

Classes of gap junction channels. Shown are three different classes of gap junction channels: homomeric channels consisting of a single connexin. heterotypic channels where homomeric hemichannels on one cell is linked to homomeric channels made from a different connexin on an adjacent cell, and heteromeric channels composed of two or more different connexins throughout. The dashed arrow indicates the channel path interconnecting the cells. (See page 20 in colour section at the back of the book)

Figure 8. Figure 8.

Differential composition of vascular gap junctions. Endothelial cells (ECs) and smooth muscle cells (SM) form three different classes of junctions. homologous junctions between ECs, homologous junctions between SMs and heterologous myoendothelial junctions. Accumulating evidence from in situ and cultured cell models suggests that Cx37 preferentially localizes to homologous junctions while Cx40 and Cx43 also localize to myoendothelial cell junctions. Relative levels of connexin expression vary by cell state and vessel type (see text). Also, whether Cx37 is expressed by SM cells is controversial. (See page 20 in colour section at the back of the book)



Figure 1.

Sequential ratiometric images are enlarged views of a single wall of each of two capillaries loaded with fura 2. A. In frame I endothelial cells are outlined and top and bottom arrows are separated by 47μm. Frames were imaged 10s apart. Note, progressive increase of Ca2+ in pacemaker (bottom arrow) generates a Ca2+ wave up the wall. The wave starts receding in frame #6. B. This capillary was treated with the gap junction inhibitor, heptanol (3mM). Note absence of Ca2+ wave, although the pacememaker (arrow) generates increase (frames #1–5) and decrease (frames #6–8) of local Ca2+

adapted from ). (See page 19 in colour section at the back of the book


Figure 2.

Influence of respiratory movements on pulmonary leukocyte kinetics. Graphs depict pulmonary arteriovenous difference in leukocyte concentration during Valsalva (left) and Muller (right) maneuver. Two patients were removed from original Valsalva data by Bierman et al. , one because of very high leukocyte counts due to leukemia, another because of incomplete sampling. Muller maneuver was only performed in 2 patients. *p < 0.05 Wilcoxon matched pairs test.



Figure 3.

Size‐dependence of leukocyte margination. Graph based on original data by Doerschuk et al. and Wiggs et al. . Extraction (mean ± SEM) refers to first passage of cells or microspheres through lungs relative to passage of red blood cells (given as zero extraction). Diameters (given as range) were calculated assuming that cells were spherical. Sigmoidal regression calculated by 4 parameter logistic curve fit.



Figure 4.

Total cell number of the circulating and pulmonary marginated pool in rabbits. Original data on total leukocytes was determined by intravital microscopy, data on PMN is from morphological studies . Data are means ± SEM. a, arterioles; v. venules.



Figure 5.

Vertical gradients of PMN retention and blood flow in the lung. 1 represents top, 6 bottom level of the lung. Percent of PMN retention in lungs of supine mongrel dogs is given in open circles, in supine rabbit lungs in open squares. In rabbits in left lateral position, regional blood flow (closed triangles) was determined by radioactive microspheres and PMN concentration (open triangles) by myeloperoxidase (MPO) assay .



Figure 6.

Leukocyte/endothelial interaction in the ventilated rabbit lung. Images were taken during ventilation with an inspiratory pressure of 8 (A) or 12 (B) mmHg. In the center of the images is a pulmonary arteriole, surrounded by several darker alveoli. Autologous leukocytes were labeled in vivo by rhodamine 6G. Arrowheads mark leukocytes firmly adherent to the vascular wall. Leukocyte accumulation in the terminal arteriolar branches at elevated inspiratory pressure is clearly visible.



Figure 7.

Classes of gap junction channels. Shown are three different classes of gap junction channels: homomeric channels consisting of a single connexin. heterotypic channels where homomeric hemichannels on one cell is linked to homomeric channels made from a different connexin on an adjacent cell, and heteromeric channels composed of two or more different connexins throughout. The dashed arrow indicates the channel path interconnecting the cells. (See page 20 in colour section at the back of the book)



Figure 8.

Differential composition of vascular gap junctions. Endothelial cells (ECs) and smooth muscle cells (SM) form three different classes of junctions. homologous junctions between ECs, homologous junctions between SMs and heterologous myoendothelial junctions. Accumulating evidence from in situ and cultured cell models suggests that Cx37 preferentially localizes to homologous junctions while Cx40 and Cx43 also localize to myoendothelial cell junctions. Relative levels of connexin expression vary by cell state and vessel type (see text). Also, whether Cx37 is expressed by SM cells is controversial. (See page 20 in colour section at the back of the book)

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Jahar Bhattacharya, Michael Koval, Wolfgang M Kuebler. The Pulmonary Microcirculation. Compr Physiol 2011, Supplement 9: Handbook of Physiology, The Cardiovascular System, Microcirculation: 712-734. First published in print 2008. doi: 10.1002/cphy.cp020415