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Am J Physiol Gastrointest Liver Physiol 293: G446-G452, 2007. First published May 17, 2007; doi:10.1152/ajpgi.00097.2007
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INFLAMMATION/IMMUNITY/MEDIATORS

PECAM-1 (CD 31) mediates transendothelial leukocyte migration in experimental colitis

Emile Rijcken, Rudolf B. Mennigen, Sebastian D. Schaefer, Mike G. Laukoetter, Christoph Anthoni, Hans-Ullrich Spiegel, Matthias Bruewer, Norbert Senninger, and Christian F. Krieglstein

Department of General Surgery, Muenster University Hospital, Germany

Submitted 23 February 2007 ; accepted in final form 16 May 2007

Transendothelial migration of circulating leukocytes into the colonic wall is a key step in the development of the inflammatory infiltrate in inflammatory bowel disease (IBD). The platelet-endothelial cell adhesion molecule-1 PECAM-1 (CD31) is expressed in the tight junction area of endothelial cells, where it is supposed to support the transmigration process. The aim of this study was to determine the role of PECAM-1 in experimental IBD and to show whether blockade of PECAM-1 has therapeutic effects. Chronic colitis was induced in female BALB/c mice by cyclic oral administration of dextran sodium sulfate (DSS) 3% (wt/vol). Expression of PECAM-1 was visualized by immunohistochemistry. In the treatment group animals received 1 mg/kg anti-PECAM-1 (2H8) ip daily starting on day 26. On day 30 leukocyte adhesion and migration was measured during N2O-isoflurane anesthesia in the distal colon by intravital microscopy. Disease activity index (DAI), histology, and MPO levels were compared with healthy and diseased controls. PECAM-1 was expressed in colitic mice. Chronic DSS colitis was characterized by a marked increase in rolling, adherent, and transmigrated leukocytes compared with healthy controls. Immunoblockade of PECAM-1 reduced leukocyte transmigration significantly and also diminished leukocyte rolling and sticking in an indirect manner. It also resulted in a significantly diminished DAI and MPO levels, as well as an amelioration of the histological inflammation score. PECAM-1 plays an important role in transendothelial leukocyte migration in DSS colitis. PECAM-1 could be a novel target for antibody-based treatment in IBD.

platelet-endothelial cell adhesion molecule-1; leukocyte transmigration; dextran sodium sulfate colitis; intravital microscopy; inflammatory bowel disease



Address for reprint requests and other correspondence: E. Rijcken, Dept. of General Surgery, Muenster Univ. Hospital, Waldeyerstrasse 1, D-48149 Muenster, Germany (e-mail: rijcken{at}uni-muenster.de)







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