title: Effect of anti-CD11b (alphaM-MAC-1) and anti-CD54 (ICAM-1) monoclonal antibodies on indomethacin induced chronic ileitis in rats.
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.
authors.affiliation: Department of General Surgery, Westfalian Wilhelm's University, Münster, Germany. kriegls@uni-muenster.de
authors.forename: C F
authors.initials: CF
authors.lastname: Krieglstein
authors.forename: C
authors.initials: C
authors.lastname: Anthoni
authors.forename: M G
authors.initials: MG
authors.lastname: Laukötter
authors.forename: E
authors.initials: E
authors.lastname: Rijcken
authors.forename: H U
authors.initials: HU
authors.lastname: Spiegel
authors.forename: N
authors.initials: N
authors.lastname: Senninger
authors.forename: G
authors.initials: G
authors.lastname: Schürmann
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D007079:Ileitis / Q000139:chemically induced / Q000276:immunology*; D007213:Indomethacin; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000276:immunology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000911:Antibodies, Monoclonal; D016861:Cyclooxygenase Inhibitors; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D007213:Indomethacin