Involvement of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the pathogenesis of granulomatous colitis in rats

Clin Exp Immunol. 2001 Nov;126(2):259-65. doi: 10.1046/j.1365-2249.2001.01690.x.

Abstract

Although increased expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) has been demonstrated in inflammatory sites of various diseases, its role in colitis remains unknown. In this study, we examined whether MAdCAM-1 is involved in the pathogenesis of granulomatous colitis induced by peptidoglycan-polysaccharide (PG-PS). Experimental colitis was induced by intramural injection of PG-PS to rat colon. After 3 weeks the colon was removed and the mucosal inflammation was assessed. The area of MAdCAM-1-positive venules and the subsets of infiltrating cells were determined in colonic mucosa by immunohistochemistry. In another experiment, monoclonal antibody against MAdCAM-1 was administered intraperitoneally to examine its attenuating effect on colitis. The intramural injection of PG-PS induced significant colonic inflammation with granuloma formation. The submucosa was drastically thickened with the infiltration of CD4 positive lymphocytes and ED-1 positive macrophages. Intense MAdCAM-1 expression was observed on endothelium of the submucosal venules in inflamed mucosa. Administration of anti-MAdCAM-1 antibody significantly attenuated the PG-PS-induced colonic damage and cell infiltration. Enhanced expression of MAdCAM-1 was demonstrated in venular endothelium of the inflamed colon in PG-PS-induced colitis. The attenuating effect of anti-MAdCAM-1 suggests the importance of the MAdCAM-1-dependent process in the formation of chronic granulomatous colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / physiology*
  • Cell Movement
  • Chronic Disease
  • Crohn Disease / chemically induced
  • Crohn Disease / etiology*
  • Crohn Disease / immunology*
  • Crohn Disease / pathology
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / pathology
  • Female
  • Immunoglobulins / physiology*
  • Immunohistochemistry
  • Intestinal Mucosa / blood supply
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • Mucoproteins / antagonists & inhibitors
  • Mucoproteins / physiology*
  • Peptidoglycan / toxicity
  • Polysaccharides / toxicity
  • Rats
  • Rats, Inbred Lew

Substances

  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • Immunoglobulins
  • Madcam1 protein, rat
  • Mucoproteins
  • Peptidoglycan
  • Polysaccharides