AJP - Heart and Circulatory Physiology, Vol 267, Issue 3 1049-H1053, Copyright © 1994 by American Physiological Society

ARTICLES

Thrombin receptor peptide-mediated leukocyte rolling in rat mesenteric venules: roles of P-selectin and sialyl Lewis X

B. J. Zimmerman, J. C. Paulson, T. S. Arrhenius, F. C. Gaeta and D. N. Granger
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130.

Neutrophil adhesion to monolayers of cultured endothelial cells is enhanced, via a P-selectin-mediated mechanism, by a 14-amino acid peptide fragment (TRP-14) of the thrombin receptor. The objective of this study was to determine whether TRP-14 promotes P-selectin-mediated sialyl Lewis X-dependent leukocyte rolling in postcapillary venules. Superfusion of the rat mesentery with TRP-14 for 30 min resulted in the recruitment of rolling leukocytes and a concomitant reduction in leukocyte rolling velocity. Analogues of TRP-14 were largely ineffective in promoting leukocyte-endothelial cell adhesion. Treatment with either a monoclonal antibody directed against rat P-selectin or soluble sialyl Lewis X oligosaccharide (the carbohydrate ligand to P-selectin found on leukocytes) 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 results also support the view that sialyl Lewis X participates in P-selectin-mediated leukocyte-endothelial cell adhesion.

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