Abstract
Leukocyte emigration from blood to sites of inflammation involves sequential interaction of specific adhesion molecules expressed by both leukocytes and endothelial cells. The central steps in leukocyte-endothelial adhesive interactions are leukocyte rolling, sticking, and transmigration. This study investigated the effect of monoclonal antibodies against CD54 (ICAM-1) and CD11b (alphaM-chain of MAC-1) on intestinal inflammation. Anti-CD54 and anti-CD11b were tested in rats with indomethacin-induced chronic ileitis. Macroscopic changes were assessed by a modified version of the Wallace et al. score. Leukocyte rolling and sticking were investigated by intravital microscopy. Results show that indomethacin administration led to a chronic inflammatory response characterized by significant increase (P<0.05) in rolling (from 5.41+/-2.87 to 32.41+/-15.03 100 microm(-1) s(-1)) and sticking (from 0.16+/-0.18 to 9.11+/-5.3 100 microm(-1) s(-1)) leukocytes. After antibody treatment only the anti-CD11b group showed significant (P<0.05) reduction in rolling (from 32.41+/-15.03 to 6.6+/-2.7 100 microm(-1) s-1) and sticking (from 9.11+/-5.3 to 0.07+/-0.09 100 microm(-1) s-1) leukocytes. This was also the case for macroscopic changes. Indomethacin led to a rise in the Wallace score from 0 to 4.29+/-0.76 points (P<0.05) and anti-CD11b to a reduction from 4.29+/-0.76 to 1.29+/-1.11 points (P<0.05). Anti-CD54 and combined anti-CD11b/CD54 administration was not followed by significant changes. Therefore we suggest that leukocyte-based CD11b but not endothelial-based CD54 contributes most to leukocyte adhesion in the setting of indomethacin-induced ileitis in rats.