Expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in acute and chronic inflammation

The objective of this study was to quantify, in vivo, constitutive and tumor necrosis factor α (TNF‐α)‐enhanced expression of mucosal addressin cell adhesion molecule‐1 (MAdCAM‐1) in different tissues from healthy wild‐type mice (C57BL/6) as well as interleukin‐10 (IL‐10)‐deficient mice with and without active colitis. Using the dual radiolabel monoclonal antibody technique, we found substantial constitutive expression of MAdCAM‐1 in the intestine, colon, and mesenteric lymph nodes. MAdCAM‐1 expression in these tissues was significantly enhanced, in a time‐dependent manner, by systemic administration of TNF‐α. Maximum surface expression was observed at 18 h after TNF‐α administration and remained significantly elevated at 48 h post‐TNF‐α injection. No significant constitutive nor TNF‐α‐induced expression of MAdCAM‐1 was detected in skeletal muscle, brain, or heart. In IL‐10‐deficient (IL‐10 k/o) mice with no clinical or histological evidence of colitis, constitutive and TNF‐α‐induced expression of MAdCAM‐1 in the intestine, cecum, and colon was not different from those values obtained with healthy wild‐type controls. IL‐10‐deficient mice with active colitis exhibited a four‐ to fivefold greater expression of MAdCAM‐1 in the cecum and colon compared with their healthy controls or to IL‐10 k/o mice with no evidence of colitis. Taken together, these data demonstrate that TNF‐α enhances surface expression of MAdCAM‐1 in intestinal and colonic tissues to the same extent in both wild‐type and IL‐10 k/o mice with no colonic inflammation, whereas IL‐10 k/o mice with active colitis exhibited a profound up‐regulation of MAd‐CAM‐1 in the colon. J. Leukoc. Biol. 65: 349–355; 1999.