4.6 Article Proceedings Paper

The P-selectin, tissue factor, coagulation triad

Journal

JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 3, Issue 8, Pages 1590-1596

Publisher

WILEY
DOI: 10.1111/j.1538-7836.2005.01373.x

Keywords

coagulation; microparticles; P-selectin; P-selectin glycoprotein ligand 1; thrombosis; tissue factor

Funding

  1. NHLBI NIH HHS [P01 HL056949, R01 HL053756, R37 HL041002, R01 HL53756, P01 HL56949, R37 HL41002] Funding Source: Medline

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The primary importance of tissue factor (TF) in blood coagulation and thrombus propagation has been recognized for many years. Nevertheless, our view about the origin of TF activity, necessary for normal hemostasis and found in pathologic conditions, needs to be revised in the light of recent observations. Pioneering work by Yale Nemerson's group showed that circulating TF on microparticles (MPs), could promote thrombus growth. The origin and characteristics of this 'blood-borne' TF are targets of intense research as well as intense debate. Surprising observations now implicate the adhesion receptor P-selectin (P-sel), known for its role in inflammation, in these MPs' generation. P-sel, translocated from granules to the cell surfaces of activated platelets and endothelial cells, was recently found to play multiple roles in hemostasis. Expressed on endothelium, it can mediate platelet rolling. Signaling by P-sel through its receptor on leukocytes, P-selectin glycoprotein ligand 1 (PSGL-1), induces the generation of TF-positive, highly procoagulant MPs. In addition, P-sel on activated platelets helps to recruit these MPs specifically to thrombi. In this review, we discuss the roles of P-sel and TF-positive MPs and highlight strategies to modulate hemostasis by modulating the P-sel, TF, coagulation triad.

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