Differential role of selectins in experimental colitis.

Abstract

The role of selectins in experimental colitis remains unknown. The aims of this study were to characterize the time-course expression of selectins in trinitrobenzene sulfonic acid (TNBS)-induced colitis, the functional role of selectins in colonic leukocyte-endothelial cell interactions, and the therapeutic usefulness of selectin blockade in this model. Control and TNBS-induced colitic rats were studied. Expression of P- and E-selectin was assessed by the radiolabeled antibody technique, and L-selectin by flow cytometry. Leukocyte-endothelial cell interactions were studied in colonic venules by using intravital microscopy under basal conditions and after P-, E-, or L-selectin immunoblockade. Additional groups of animals were treated with anti-P-selectin antibody, a nonbinding antibody, or dexamethasone, for 7 days. P-selectin and E-selectin expression were markedly up-regulated in colitic rats. Increased leukocyte rolling was abrogated by anti-P-selectin, but only attenuated by anti-E- or anti-L-selectin antibodies. Only pretreatment with anti-P- selectin decreased leukocyte adhesion. Animals chronically treated with dexamethasone, but not with anti- P-selectin, had significantly lower macroscopic and histologic damage scores, colon weight, and myeloperoxidase (MPO) activity than those treated with nonbinding antibody. P-selectin plays a key role on leukocyte rolling and its blockade attenuates leukocyte adhesion in TNBS-induced colitis. However, treatment with an anti-P-selectin antibody does not significantly improve colitis.