Role of P-selectin and intercellular adhesion molecule-1 in TNB-induced colitis in rats.

It has been proposed that neutrophil-endothelial cell interactions mediated by adhesion molecules are involved in the pathogenesis of inflammatory bowel disease. The objective of the present study was to determine the effects of monoclonal antibodies (MAbs) directed against endothelial adhesion molecules, P-selectin and intercellular adhesion molecule-1 (ICAM-1), in rats with colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNB). Colonic inflammation was induced by administering an enema of TNB dissolved in 50% ethanol (120 mg/ml) to male Wistar rats (at a total volume of 0.25 ml per rat) after a 48-hour fast. Anti-P-selectin MAb or anti-ICAM-1 MAb was injected via the tail vein at a dose of 1 mg/kg after the induction of colitis. Rats in the control group received nonbinding mouse immunoglobulin G1. The plasma level of soluble P-selectin showed an increase within 48 h after the TNB enema. Colonic inflammation was assessed at 1 week after TNB administration. The colonic damage score and the wet weight of the colon were significantly decreased by treatment with either MAb. The increase of myeloperoxidase (MPO) activity, an index of neutrophil accumulation, and the increase of thiobarbituric acid-reactive substances (TBA-RS), an index of lipid peroxidation, in the colonic mucosa were inhibited by both MAbs. These results suggest that neutrophil-endothelial cell interactions via P-selectin and ICAM-1 play an important role in the development of TNB-induced colitis in rats. Copyright 2001 S. Karger AG, Basel