Pathomechanism of Cellular Infiltration in the Perivascular Region of Several Organs in SAMP1/Yit Mouse

Abstract

ABSTRACT. We investigated the histological changes of extra-intestinal organs, such as the liver, kidney, lung and pancreas in SAMP1/ Yit mice, a human Crohn's disease model, using immunohistochemical techniques. The perivascular cellular infiltration was detected around the small vessels after 30 weeks. These infiltrating cells consisted of many CD4-positive T-lymphocytes, and small numbers of CD8-positive T-lymphocytes and IgG-positive B-lymphocytes. MAdCAM-1 and VCAM-1 were detected in vascular endothelial cells in non-affected regions of 13 and 20 week-old, as well as in the affected regions showing perivascular cellular infiltration after 30 weeks. In addition, integrin 47 was detected on these infiltrating cells in the perivascular regions after 30 week-old. LT- and IL-12, cytokines of the Th-1-type immune response, were not observed in these affected regions. However, IL-4, one of the cytokines of the Th-2-type immune response, was detected on the perivascular infiltrating cells after 30 week-old. These results revealed that the changes in extra-intestinal organs were mainly caused by infiltration of CD4-positive T-lymphocytes into the perivascular regions in SAMP1/Yit mice. These cellular infiltrations were thought to be initiated by adhesion of CD4-positive T-lymphocytes to the endothelial cells mediated by MAdCAM-1 and integrin 7. Immunohistochemistry for Th related cytokines indicated that the perivascular cellular infiltration was developed by the Th-2-type immune response in the extra-intestinal organs of SAMP1/Yit mouse.KEY WORDS: cell infiltration, pathomechanism, SAMP1/Yit mouse.

Increased glycolysis affects β-cell function and identity in aging and diabetes

“…Notably, we observed perivascular infiltration of mononuclear cells in exocrine regions of 59- and 86-week-old P1, which tested positive for CD45 ( Supplementary Figure 3 , red arrows). This is consistent with a previous report showing infiltration of T-lymphocytes in multiple organs in aged P1 [ 30 ].…”

Anatomy, pathophysiology and basic mechanisms of disease

“…357 The chronically inflamed liver also expresses mucosal addressin cell adhesion molecules (MAdCAM-1) on the portal vein and sinusoidal endothelium, serving as an additional stimulus for homing of T-lymphocytes directly to the portal tract. 358,359 The role of MAdCAM-1 in inducing intrahepatic inflammation may be particularly relevant in liver disease associated with inflammatory diseases of the gut. Neo-expression of lymphotoxin-β and its cognate receptor is also likely to play a role in the formation of lymphoid aggregates within portal tracts, particularly in hepatitis C infection.…”

Ultrasound-based molecular imaging and specific gene delivery to mesenteric vasculature by endothelial adhesion molecule targeted microbubbles in a mouse model of Crohn's disease

“…Animal studies suggest that CD in time takes on characteristics of chronic inflammatory disease, such as continuously dysregulated production of pro-inflammatory cytokines, overexpression of adhesion molecules such as mucosal addressin cell adhesion molecule-1 (MAdCAM-1) [13,15], intercellular adhesion molecule-1 (ICAM-1) [12,16,17], and in some models, vascular adhesion molecule-1 (VCAM-1) [18,19]. Notably, increased expression of MAdCAM-1 has been reported in the intestinal microvascular endothelium in several CD-like mouse models [20,21], as has VCAM-1 [22]. …”