To cite this article: Polgar J, Matuskova J, Wagner DD. The P-selectin, tissue factor, coagulation triad. J Thromb Haemost 2005; 3: 1590-6.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 Ôblood-borneÕ 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 MPsÕ 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.Keywords: coagulation, microparticles, P-selectin, P-selectin glycoprotein ligand 1, thrombosis, tissue factor. P-selectin -link between inflammation and hemostasis P-selectin (P-sel) is a member of the selectin family of cell adhesion receptors, which mediate binding to specific carbohydrate-containing ligands [1]. Selectins mediate adhesion among leukocytes, platelets, and endothelium. P-sel, the largest member of the selectin family, is localized in the membranes of platelet a-granules [2] and in storage granules of endothelial cells called Weibel-Palade bodies [3,4] (Fig. 1). The major component of Weibel-Palade bodies is von Willebrand factor (VWF) [5]. VWF plays two main functions in hemostasis: it mediates platelet adhesion to the injured vessel wall, and it carries coagulation factor VIII. VWF directs the formation of the Weibel-Palade bodies and, in its absence, P-sel is mislocalized in the endothelial cell [6]. Weibel-Palade body exocytosis is triggered by secretagogues such as thrombin and histamine and occurs within seconds to minutes after stimulation. Similarly in platelets, upon activation, P-sel translocates with the a-granule membrane to the cell surface. Once present on the cell surface, the receptor can mediate cellular adhesion.A key role of P-sel is in mediating leukocyte interactions in inflammation [2]. P-sel has long been known to support leukocyte rolling, as shown in vitro [7] and in vivo [8]. The most clearly defined ligand for P-sel is P-selectin glycoprotein ligand 1 (PSGL-1). It is a homodimeric mucin expressed on the majority of leukocytes...

Objective-High-density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), mediated cellular uptake of lipoprotein cholesterol controls HDL structure and plasma HDL and biliary cholesterol levels. In SR-BI knockout (KO) mice, an unusually high plasma unesterified-to-total cholesterol ratio (UC:TC) and abnormally large HDL particles apparently contribute to pathology, including female infertility, susceptibility to atherosclerosis and coronary heart disease, and anemia. Here we examined the influence of SR-BI deficiency on platelets. Methods and Results-The high plasma UC:TC ratio in SR-BI KO mice was correlated with platelet abnormalities, including high cholesterol content, abnormal morphologies, high clearance rates, and thrombocytopenia. One day after platelets from wild-type mice were infused into SR-BI KO mice, they exhibited abnormally high cholesterol content and clearance rates similar to those of endogenous platelets. Platelets from SR-BI KO mice exhibited in vitro a blunted aggregation response to the agonist ADP but a normal response to PAR4. Conclusions-In

No abstract