Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin.
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.
Falati
Shahrokh
S
Center for Hemostasis and Thrombosis Research, Research East 319, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
Liu
Qingde
Q
Gross
Peter
P
Merrill-Skoloff
Glenn
G
Chou
Janet
J
Vandendries
Erik
E
Celi
Alessandro
A
Croce
Kevin
K
Furie
Barbara C
BC
Furie
Bruce
B
D000818:Animals; D001777:Blood Coagulation; D004730:Endothelium, Vascular / Q000293:injuries; D007834:Lasers; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000378:metabolism; D008856:Microscopy, Fluorescence; D019007:P-Selectin / Q000097:blood*; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood* / Q000209:etiology*
D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D013925:Thromboplastin