MONOCLONAL-ANTIBODIES SPECIFIC FOR BETA(7) INTEGRIN AND MUCOSAL ADDRESSIN CELL-ADHESION MOLECULE-1 (MADCAM-1) REDUCE INFLAMMATION IN THE COLON OF SCID MICE RECONSTITUTED WITH CD45RB(HIGH) CD4(-CELLS() T)

Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is an adhesion p rotein expressed on endothelium in mucosal tissues that has been shown to play an important role in the selective homing of lymphocytes to i ntestinal mucosa and associated lymphoid tissue. To determine whether MAdCAM-1 or its ligand alpha(4) beta(7) would be appropriate targets f or therapeutic intervention in gut-associated inflammation, we tested the ability of rat mAbs specific for beta(7) integrin and MAdCAM-1 to inhibit chronic colonic inflammation in scid mice reconstituted with C D4(+) T cells enriched for the CD45RB(high) subpopulation. Abs specifi c for beta(7) and MAdCAM-1 blocked recruitment of lymphocytes to the c olitic colon, and more importantly, these Abs significantly reduced th e severity of colonic inflammatory disease in this animal model. There fore, the adhesive interactions mediated by alpha(4) beta(7) and MAdCA M are intimately involved in leukocyte recruitment to gut in chronic i nflammatory disease and may be relevant therapeutic targets for patien ts with inflammatory bowel disease.