PLATELET-ENDOTHELIAL INTERACTIONS IN INFLAMED MESENTERIC VENULES

The selectins are membrane glycoproteins promoting adhesive events bet ween 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 mediat ing platelet-endothelial interactions during inflammation. We demonstr ate, using intravital microscopic examination of venules inflamed with tumor necrosis factor-alpha (TNF-alpha), that resting platelets inter act with both P- and E-selectins and that the leukocyte alpha(1,3)fuco syltransferases FucT IV and FucT VII do not provide platelets with sel ectin ligand activity. We also show that after thrombin activation of wild-type (+/+) platelets, platelet P-selectin can mediate interaction s on a TNF-alpha-inducible endothelial ligand. To evaluate the potenti al role of platelet P-selectin in the recruitment of leukocytes to inf lammatory sites, we reconstituted the bone marrow of mice deficient in both P- and E-selectins (P/E-/-) with wild-type (+/+) or P-selectin-d eficient (P-/-) bone marrow containing megakaryocytic precursors. Prov iding +/+ platelets to P/E-/- mice by bone marrow transplantation did not rescue the immunodeficient phenotype. suggesting that platelet P-s electin does not have an active function in the recruitment of leukocy tes into inflammatory sites. To participate in inflammatory or hemosta tic responses, platelets may use the endothelial selectins. (C) 1998 b y The American Society of Hematology.