Accumulation of Tissue Factor Into Developing Thrombi in Vivo Is Dependent Upon Microparticle P-selectin Glycoprotein Ligand 1 and Platelet P-selectin

J Exp Med. 2003 Jun 2;197(11):1585-98. doi: 10.1084/jem.20021868.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Coagulation
  • Endothelium, Vascular / injuries
  • Lasers
  • Lipopolysaccharide Receptors / blood
  • Male
  • Membrane Glycoproteins / blood*
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microcirculation / metabolism
  • Microscopy, Fluorescence
  • P-Selectin / blood*
  • Thromboplastin / metabolism*
  • Thrombosis / blood*
  • Thrombosis / etiology*

Substances

  • Lipopolysaccharide Receptors
  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Thromboplastin