Platelet-endothelial interactions in inflamed mesenteric venules

The selectins are membrane glycoproteins promoting adhesive events between leukocytes, platelets. and endothelial cells. We have previously demonstrated that platelets roll on P-selectin expressed on stimulated endothelium. In this study. we wished to examine the function of both the platelet and endothelial selectins, P- and E-selectins. in mediating platelet-endothelial interactions during inflammation. We demonstrate, using intravital microscopic examination of venules inflamed with tumor necrosis factor-alpha (TNF-alpha), that resting platelets interact with both P- and E-selectins and that the leukocyte alpha(1,3)fucosyltransferases FucT IV and FucT VII do not provide platelets with selectin ligand activity. We also show that after thrombin activation of wild-type (+/+) platelets, platelet P-selectin can mediate interactions on a TNF-alpha-inducible endothelial ligand. To evaluate the potential role of platelet P-selectin in the recruitment of leukocytes to inflammatory sites, we reconstituted the bone marrow of mice deficient in both P- and E-selectins (P/E-/-) with wild-type (+/+) or P-selectin-deficient (P-/-) bone marrow containing megakaryocytic precursors. Providing +/+ platelets to P/E-/- mice by bone marrow transplantation did not rescue the immunodeficient phenotype. suggesting that platelet P-selectin does not have an active function in the recruitment of leukocytes into inflammatory sites. To participate in inflammatory or hemostatic responses, platelets may use the endothelial selectins. (C) 1998 by The American Society of Hematology.