HUMAN MUCOSAL ADDRESSIN CELL-ADHESION MOLECULE-1 IS PREFERENTIALLY EXPRESSED IN INTESTINAL-TRACT AND ASSOCIATED LYMPHOID-TISSUE

Lymphocyte homing to normal tissues and recruitment to inflammatory ti ssue sites are controlled, in part, by the selective expression of che mokines, pro-inflammatory cytokines and mediators, and various adhesio n proteins and molecules. In the mouse, mucosal addressin cell adhesio n molecule-1 (MAdCAM-1) is selectively expressed on endothelium of hig h endothelial venules in gut and gut-associated lymphoid tissue. By in teraction with its integrin ligand, alpha 4 beta 7, lymphocytes presum ed to be involved in mucosal immunity are selectively recruited to the se intestinal sites. After generating monoclonal antibodies against a murine cell line expressing recombinant human MAdCAM-1, we qualitative ly and semiquantitatively assessed MAdCAM-1 expression in human tissue sections from various normal and inflammatory disorders. We found tha t human MAdCAM-1, as in the mouse, is expressed in a tissue-selective manner. In normal tissues, MAdCAM-1 is constitutively expressed to end othelium of venules of intestinal lamina propria. Interestingly, using computer-assisted morphometric analysis, the proportion of venular en dothelium within lamina propria that expresses MAdCAM-1 is increased, compared with normal tissues, at inflammatory foci associated with ulc erative colitis and Crohn's disease. Moreover, for the most part, MAdC AM-1 is not detected in the majority of normal or inflamed extra-intes tinal tissues, including those with mucosal surfaces. These results ar e consistent with a role, as originally defined in the mouse, for huma n MAdCAM-1 in the localization of alpha 4 beta 7(+) lymphocytes in the gastrointestinal tract and associated lymphoid tissue. As such, the p athway defined by MAdCAM-1/alpha 4 beta 7 may be a relevant tissue-spe cific therapeutic target for the modulation of inflammatory bowel dise ase activity.