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 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.
Zimmerman
B J
BJ
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130.
Paulson
J C
JC
Arrhenius
T S
TS
Gaeta
F C
FC
Granger
D N
DN
D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D009844:Oligosaccharides / Q000378:metabolism*; D019007:P-Selectin; D010446:Peptide Fragments / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018179:Receptors, Thrombin / Q000502:physiology*; D000080506:Sialyl Lewis X Antigen; D013152:Splanchnic Circulation; D014699:Venules
D000911:Antibodies, Monoclonal; D009844:Oligosaccharides; D019007:P-Selectin; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; D018179:Receptors, Thrombin; D000080506:Sialyl Lewis X Antigen; C089243:thrombin receptor peptide 14