THROMBIN RECEPTOR PEPTIDE-MEDIATED LEUKOCYTE ROLLING IN RAT MESENTERIC VENULES - ROLES OF P-SELECTIN AND SIALYL-LEWIS-X

Neutrophil adhesion to monolayers of cultured endothelial cells is enh anced, via a P-selectin-mediated mechanism, by a 14-amino acid peptide fragment (TRP-14) of the thrombin receptor. The objective of this stu dy was to determine whether TRP-14 promotes P-selectin-mediated sialyl Lewis X-dependent leukocyte rolling in postcapillary venules. Superfu sion of the rat mesentery with TRP-14 for 30 min resulted in the recru itment of rolling leukocytes and a concomitant reduction in leukocyte rolling velocity. Analogues of TRP-14 were largely ineffective in prom oting leukocyte-endothelial cell adhesion. Treatment with either a mon oclonal antibody directed against rat P-selectin or soluble sialyl Lew is X oligosaccharide (the carbohydrate ligand to P-selectin found on l eukocytes) significantly attenuated the TRP-14-induced recruitment of rolling leukocytes. However, no effect was observed with a nonbinding antibody or a control fucose-deficient oligosaccharide. These results indicate that TRP-14 elicits the recruitment of rolling leukocytes in postcapillary venules via a P-selectin-dependent mechanism. The result s also support the view that sialyl Lewis X participates in P-selectin -mediated leukocyte-endothelial cell adhesion.