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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2334-2339.
Prepublished online as a Blood First Edition Paper on June 14, 2005; DOI 10.1182/blood-2005-04-1530.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Activated platelets induce Weibel-Paladebody secretion and leukocyte rolling in vivo: role of P-selectin
Vandana S. Dole,
Wolfgang Bergmeier,
Heather A. Mitchell,
Sarah C. Eichenberger, and
Denisa D. Wagner
From the CBR Institute for Biomedical Research, and the Department of Pathology, Harvard Medical School, Boston, MA
The presence of activated platelets and platelet-leukocyte aggregates in the circulation accompanies major surgical procedures and occurs in several chronic diseases. Recent findings that activated platelets contribute to the inflammatory disease atherosclerosis made us address the question whether activated platelets stimulate normal healthy endothelium. Infusion of activated platelets into young mice led to the formation of transient platelet-leukocyte aggregates and resulted in a several-fold systemic increase in leukocyte rolling 2 to 4 hours after infusion. Rolling returned to baseline levels 7 hours after infusion. Infusion of activated P-selectin-/- platelets did not induce leukocyte rolling, indicating that platelet P-selectin was involved in the endothelial activation. The endothelial activation did not require platelet CD40L. Leukocyte rolling was mediated solely by the interaction of endothelial P-selectin and leukocyte P-selectin glycoprotein ligand 1 (PSGL-1). Endothelial P-selectin is stored with von Willebrand factor (VWF) in Weibel-Palade bodies. The release of Weibel-Palade bodies on infusion of activated platelets was indicated by both elevation of plasma VWF levels and by an increase in the in vivo staining of endothelial P-selectin. We conclude that the presence of activated platelets in circulation promotes acute inflammation by stimulating secretion of Weibel-Palade bodies and P-selectinmediated leukocyte rolling.

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