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

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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.