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

By S. Falati, Qingde Liu, P. Gross, Glenn Merrill-Skoloff, J. Chou, E. Vandendries, A. Celi, K. Croce, B. Furie, Bruce Furie. Journal of Experimental Medicine, 2003

785 citations recorded by the source corpus.

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.

Subfields: Hematology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/101749f1afb0855b78f6d30a700e1d9ab361bae8

How researchers see this paper

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In Hematology

1. M. Levi
2. H. Versteeg
3. Pieter H. Reitsma
4. J. Heemskerk
5. C. Esmon
6. D. Lyden

In Immunology and Allergy

1. María Yáñez-Mó
2. Zoraida Andreu
3. W. Stoorvogel

Citations in the corpus

• Focus on Extracellular Vesicles: Introducing the Next Small Big Thing (2016, neutral): “, GPIb, GPIIb–IIIa and P-selectin [32–35], and integrins, e.”
• Extracellular vesicles in cancer: cell-to-cell mediators of metastasis (2016, background): “In vivo, TF-containing EVs released by monocytes bind to activated platelets and promote the generation of arterial thrombi (Falati et al., 2003).”
• Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives (2011, background): “The importance of microparticles, TF, and P-selectin/E-selectin in venous stasis-induced thrombosis has also been shown in the developing thrombus in mouse arterioles induced by endothelial injury model (173).”
• New fundamentals in hemostasis. (2013, background): “Platelets appear to acquire TF through interaction with TF-bearing microparticles from monocytes (70, 88, 127), but platelets also contain TF pre-mRNA, which can be spliced into mature mRNA upon platelet activation, culminating in limited TF protein expression and procoagulant activity (267).”
• The interactions between inflammation and coagulation (2005, background): “In vivo (Palabrica et al, 1992; Falati et al, 2003) at wound sites and on artificial surfaces (Giesen et al, 1999; Rauch et al, 2000), blood-borne tissue factor seems to be responsible for the propagation of the thrombus.”
• Biological properties of extracellular vesicles and their physiological functions (2015, background): “Activated monocytes (336,349,350) shed TF EVs (351,352) and neutrophils may also contribute (353).”
• Membrane microparticles: two sides of the coin. (2005, background): “This indicates one pathway for the initiation of blood coagulation involving the accumulation of TF-containing MPs in the platelet thrombus (15).”
• Defective thrombus formation in mice lacking coagulation factor XII (2005, background): “These particles can be incorporated into a growing thrombus in a P-selectin–dependent manner (29).”