Platelet-endothelial interactions in inflamed mesenteric venules

• Published in: Blood Vol. 91; no. 4; pp. 1318 - 1324
• Main Authors: FRENETTE, P. S, MOYNA, C, HARTWELL, D. W, LOWE, J. B, HYNES, R. O, WAGNER, D. D
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15-02-1998
• Subjects: Animals; Biological and medical sciences; Blood coagulation. Blood cells; Blood Platelets - metabolism; Blood Platelets - pathology; Cell Adhesion; Cell Movement; E-Selectin - physiology; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods, hemostasis, fibrinolysis; Inflammation - pathology; Male; Mice; Mice, Inbred C57BL; Molecular and cellular biology; P-Selectin - physiology; Splanchnic Circulation; Venules - pathology; Endothelial cell; Cytokine; Rodentia; Cell adhesion molecule; Cell cell interaction; Inflammation; Mesentery; Venule; P Selectin; Vertebrata; Platelet; Mammalia; Mouse; Hemostasis; Animal; Tumor necrosis factor α
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v91.4.1318

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.