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

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.

• Authors: R Hokari, S Kato, K Matsuzaki, A Iwai, A Kawaguchi, S Nagao, T Miyahara, K Itoh, E Sekizuka, H Nagata, H Ishii, T Iizuka, M Miyasaka, S Miura
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 126 Issue 2 Pg. 259-65 (Nov 2001) ISSN: 0009-9104 [Print] England
• PMID: 11703369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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