The P‐selectin, tissue factor, coagulation triad

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 observ...

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Bibliographic Details
Published in:Journal of thrombosis and haemostasis 2005-08, Vol.3 (8), p.1590-1596
Main Authors: POLGAR, J., MATUSKOVA, J., WAGNER, D. D.
Format: Article
Language:English
Subjects:
Animals
Blood Coagulation - physiology
Blood Coagulation Tests
Coagulants - metabolism
coagulation
Hemostasis
Humans
Inflammation
Leukocytes - cytology
Membrane Glycoproteins - metabolism
Mice
microparticles
Microscopy, Electron
Models, Biological
P-Selectin - metabolism
Protein Transport
P‐selectin
P‐selectin glycoprotein ligand 1
Thromboplastin - metabolism
thrombosis
Time Factors
tissue factor
Umbilical Veins - cytology
Umbilical Veins - ultrastructure
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Summary: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.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/j.1538-7836.2005.01373.x