Falati, ShahrokhLiu, QingdeGross, PeterMerrill-Skoloff, GlennChou, JanetVandendries, ErikCeli, AlessandroCroce, KevinFurie, Barbara C.Furie, Bruce2019-10-052003Falati, Shahrokh, Qingde Liu, Peter Gross, Glenn Merrill-Skoloff, Janet Chou, Erik Vandendries, Alessandro Celi, Kevin Croce, Barbara C. Furie, and Bruce Furie. 2003. “Accumulation of Tissue Factor into Developing Thrombi In Vivo Is Dependent upon Microparticle P-Selectin Glycoprotein Ligand 1 and Platelet P-Selectin.” The Journal of Experimental Medicine 197 (11): 1585–98. https://doi.org/10.1084/jem.20021868.0022-10071540-9538http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483177Using 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.en-USJournal Article2019-10-0510.1084/jem.20021868