Comprehensive Physiology Wiley Online Library

Gastrointestinal and Liver Microcirculations: Roles in Inflammation and Immunity

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Introduction
2 Gastrointestinal Microcirculation
2.1 Microvascular perfusion and inflammation
2.2 Microvascular perfusion and the recruitment of leukocytes and platelets
3 The Microcirculation and Immune Function
3.1 Lymphocyte homing and cellular traffic in organized lymphoid tissue of intestine
3.2 Lymphoid cell traffic to intestinal immune effector sites
3.3 The microcirculation and IBD
3.4 NSAIDs: the microcirculation and neutrophil‐mediated GI injury
3.5 Helicobacter pylori (HP) infection and gastric mucosal injury
4 Liver Microcirculation
4.1 Role of inflammatory cells in liver disease
Figure 1. Figure 1.

Relationship between shear rate and the adhesion of leukocytes and platelets in rat mesenteric venules. Data from Am J Physiol 284: G123–G129. 2003.

Figure 2. Figure 2.

Schematic representation of the T lymphocyte trafficking in the intestinal immune system. The organized lymphoid tissues of the Peyer's patches (PP) and mesenteric lymph nodes (MLNs) are involved in the induction of immunity and education of intestinal tropism of lymphocytes. Naïve and central memory T lymphocytes and plasmacytoid dendritic cells (DC) migrate into PP through high endothelium of postcapillary venules (PCV). Central and effector memory T cells also migrate to the effector sites in the lamina propria of the intestine. The cell adhesion molecules used for the recruitment of lymphoid cells are shown in the frame. (See page 18 in colour section at the back of the book)

Figure 3. Figure 3.

Representative microscopic images of lymphocyte migration in the rat intestine. (A) An ileal Peyer's patch (PP) under fluorescence microscopy at 20 min after the infusion of carboxyfluorescein succinimidyl ester (CFSE)‐labeled T lymphocytes derived from intestinal lymph. The lymphocytes adhere in a relatively select portion of postcapillary venules of PP (× 10 objective lens). (B) Distribution of transmigrated CFSE‐labeled T lymphocytes in PP 1 h after the infusion. Many lymphocytes migrate into the interstitium (× 20 objective lens). (C) High‐speed video images of rat intestinal collecting lymphatics. A marked increase in lymphocyte transport through lymphatics is observed 4h after administration of olive oil. (D) Villus tips of ileal mucosa in endotoxin‐treated rats under fluorescence microscopy. Adherent T lymphocytes in arcade microvessels are observed 20 min after T lymphocyte administration (× 20 objective lens). (See page 18 in colour section at the back of the book)

Figure 4. Figure 4.

Chemokine and chemokine receptor expression in the intestinal mucosa and their possible roles in the trafficking of lymphocytes and plasma cells. Chemokine expression in organized lymphoid tissues (e.g. Peyer's patches) differs from that observed in the intestinal mucosa, and is characterized by the expression of SLC/CCL21 and CCL19/ELC in the high endothelial venules for attracting T cells and CXCL13/BLC for B cells. The small intestine expresses the specific chemokine CCL25/TECK. which attracts cells with small intestinal tropism such as CCR9+ memory T cells and CCR9+ plasma cells. During intestinal inflammation, the mechanisms controlling lymphocyte trafficking become more complex. (See page 19 in colour section at the back of the book)

Figure 5. Figure 5.

(A) illustrates that leukocytes roll in post‐sinusoidal venules due to [I] expression of adhesion molecules, and diameter is not a limitation. (B) illustrates that leukocytes approach the diameter of sinusoids and the lack of selectins within these vessels prevent rolling. Only firm adhesion is seen in sinusoids.

Figure 6. Figure 6.

The role of selectins in leukocyte adhesion in sinusoids (A) and hepatic venules (B) after FMLP treatment. Liver preparations were studied in wildtype, P‐selectin defecient, and double E‐selectin/P‐selectin deficient mice. To eliminate contributions of all three selectins, some E‐selectin/P‐selectin defecient animals were also given an anti‐L‐selectin mAb intravenously (Mel‐14, 3mg/kg). Preparations were superfused continuously with bicarbonate‐buffered saline alone or 10 uM FMLP. Leukocyte adhesion was determined 60 min after FMLP treatment. Data are represented as means ± SEM. *p < 0.05 vs. wildtype; n = 18.



Figure 1.

Relationship between shear rate and the adhesion of leukocytes and platelets in rat mesenteric venules. Data from Am J Physiol 284: G123–G129. 2003.



Figure 2.

Schematic representation of the T lymphocyte trafficking in the intestinal immune system. The organized lymphoid tissues of the Peyer's patches (PP) and mesenteric lymph nodes (MLNs) are involved in the induction of immunity and education of intestinal tropism of lymphocytes. Naïve and central memory T lymphocytes and plasmacytoid dendritic cells (DC) migrate into PP through high endothelium of postcapillary venules (PCV). Central and effector memory T cells also migrate to the effector sites in the lamina propria of the intestine. The cell adhesion molecules used for the recruitment of lymphoid cells are shown in the frame. (See page 18 in colour section at the back of the book)



Figure 3.

Representative microscopic images of lymphocyte migration in the rat intestine. (A) An ileal Peyer's patch (PP) under fluorescence microscopy at 20 min after the infusion of carboxyfluorescein succinimidyl ester (CFSE)‐labeled T lymphocytes derived from intestinal lymph. The lymphocytes adhere in a relatively select portion of postcapillary venules of PP (× 10 objective lens). (B) Distribution of transmigrated CFSE‐labeled T lymphocytes in PP 1 h after the infusion. Many lymphocytes migrate into the interstitium (× 20 objective lens). (C) High‐speed video images of rat intestinal collecting lymphatics. A marked increase in lymphocyte transport through lymphatics is observed 4h after administration of olive oil. (D) Villus tips of ileal mucosa in endotoxin‐treated rats under fluorescence microscopy. Adherent T lymphocytes in arcade microvessels are observed 20 min after T lymphocyte administration (× 20 objective lens). (See page 18 in colour section at the back of the book)



Figure 4.

Chemokine and chemokine receptor expression in the intestinal mucosa and their possible roles in the trafficking of lymphocytes and plasma cells. Chemokine expression in organized lymphoid tissues (e.g. Peyer's patches) differs from that observed in the intestinal mucosa, and is characterized by the expression of SLC/CCL21 and CCL19/ELC in the high endothelial venules for attracting T cells and CXCL13/BLC for B cells. The small intestine expresses the specific chemokine CCL25/TECK. which attracts cells with small intestinal tropism such as CCR9+ memory T cells and CCR9+ plasma cells. During intestinal inflammation, the mechanisms controlling lymphocyte trafficking become more complex. (See page 19 in colour section at the back of the book)



Figure 5.

(A) illustrates that leukocytes roll in post‐sinusoidal venules due to [I] expression of adhesion molecules, and diameter is not a limitation. (B) illustrates that leukocytes approach the diameter of sinusoids and the lack of selectins within these vessels prevent rolling. Only firm adhesion is seen in sinusoids.



Figure 6.

The role of selectins in leukocyte adhesion in sinusoids (A) and hepatic venules (B) after FMLP treatment. Liver preparations were studied in wildtype, P‐selectin defecient, and double E‐selectin/P‐selectin deficient mice. To eliminate contributions of all three selectins, some E‐selectin/P‐selectin defecient animals were also given an anti‐L‐selectin mAb intravenously (Mel‐14, 3mg/kg). Preparations were superfused continuously with bicarbonate‐buffered saline alone or 10 uM FMLP. Leukocyte adhesion was determined 60 min after FMLP treatment. Data are represented as means ± SEM. *p < 0.05 vs. wildtype; n = 18.

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Soichiro Miura, Paul Kubes, D Neil Granger. Gastrointestinal and Liver Microcirculations: Roles in Inflammation and Immunity. Compr Physiol 2011, Supplement 9: Handbook of Physiology, The Cardiovascular System, Microcirculation: 684-711. First published in print 2008. doi: 10.1002/cphy.cp020414