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Platelet-Endothelial Interactions in Inflamed Mesenteric Venules
Paul S. Frenette,
Caitlin Moyna,
Daqing W. Hartwell,
John B. Lowe,
Richard O. Hynes, and
Denisa D. Wagner
From the Center for Blood Research, Departments of Pathology and
Medicine, Harvard Medical School, Boston; Howard Hughes Medical
Institute, Center for Cancer Research, Department of Biology,
Massachusetts Institute of Technology, Cambridge, MA; and Howard Hughes
Medical Institute, University of Michigan Medical School, Ann
Arbor, MI.
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- (TNF-), that
resting platelets interact with both P- and E-selectins and that the
leukocyte (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--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.
Blood, Vol. 91 No. 4 (February 15), 1998:
pp. 1318-1324
© 1998 by The American Society of Hematology.
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