Involvement of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the pathogenesis of granulomatous colitis in rats.
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.
Hokari
R
R
Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Kato
S
S
Matsuzaki
K
K
Iwai
A
A
Kawaguchi
A
A
Nagao
S
S
Miyahara
T
T
Itoh
K
K
Sekizuka
E
E
Nagata
H
H
Ishii
H
H
Iizuka
T
T
Miyasaka
M
M
Miura
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000502:physiology*; D002465:Cell Movement; D002908:Chronic Disease; D003424:Crohn Disease / Q000139:chemically induced / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D005260:Female; D007136:Immunoglobulins / Q000502:physiology*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D009088:Mucoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D010457:Peptidoglycan / Q000633:toxicity; D011134:Polysaccharides / Q000633:toxicity; D051381:Rats; D011917:Rats, Inbred Lew
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C504268:Madcam1 protein, rat; D009088:Mucoproteins; D010457:Peptidoglycan; D011134:Polysaccharides