The Journal of Experimental Medicine
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Published 2 June 2003. doi:10.1084/jem.20021868
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© Rockefeller University Press, 0022-1007/2003/6/1585 $5.00
The Journal of Experimental Medicine, Volume 197, Number 11, 1585-1598

Accumulation of Tissue Factor into Developing Thrombi In Vivo Is Dependent upon Microparticle P-Selectin Glycoprotein Ligand 1 and Platelet P-Selectin

Shahrokh Falati, Qingde Liu, Peter Gross, Glenn Merrill-Skoloff, Janet Chou, Erik Vandendries, Alessandro Celi, Kevin Croce, Barbara C. Furie and Bruce Furie

Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215

Address correspondence to Bruce Furie, Center for Hemostasis and Thrombosis Research, Research East 319, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. Phone: 617-667-0620; Fax: 617-975-5505; E-mail: bfurie{at}caregroup.harvard.edu

Using a laser-induced endothelial injury model, we examined thrombus formation in the microcirculation of wild-type and genetically altered mice by real-time in vivo microscopy to analyze this complex physiologic process in a system that includes the vessel wall, the presence of flowing blood, and the absence of anticoagulants. We observe P-selectin expression, tissue factor accumulation, and fibrin generation after platelet localization in the developing thrombus in arterioles of wild-type mice. However, mice lacking P-selectin glycoprotein ligand 1 (PSGL-1) or P-selectin, or wild-type mice infused with blocking P-selectin antibodies, developed platelet thrombi containing minimal tissue factor and fibrin. To explore the delivery of tissue factor into a developing thrombus, we identified monocyte-derived microparticles in human platelet–poor plasma that express tissue factor, PSGL-1, and CD14. Fluorescently labeled mouse microparticles infused into a recipient mouse localized within the developing thrombus, indicating that one pathway for the initiation of blood coagulation in vivo involves the accumulation of tissue factor– and PSGL-1–containing microparticles in the platelet thrombus expressing P-selectin. These monocyte-derived microparticles bind to activated platelets in an interaction mediated by platelet P-selectin and microparticle PSGL-1. We propose that PSGL-1 plays a role in blood coagulation in addition to its known role in leukocyte trafficking.

Key Words: blood coagulation • fibrin • thrombosis • endothelium • intravital microscopy


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