Human platelets synthesize and express functional tissue factor

Abstract

The source and significance of blood-borne tissue factor (TF) are controversial. TF mRNA, protein, and TF-dependent procoagulant activity (PCA) have been detected in human platelets, but direct evidence of TF synthesis is missing. Nonstimulated monocyte-free plate-lets from most patients expressed TF mRNA, which was enhanced or induced in all of them after platelet activation. Immunoprecipitation assays revealed TF protein (mainly of a molecular weight [Mr] of approximately 47 kDa, with other bands of approximately 35 and approximately 60 kDa) in nonstimulated platelet membranes, which also increased after activation. This enhancement was con-comitant with TF translocation to the plasma membrane, as demonstrated by immunofluorescence-confocal micros-copy and biotinylation of membrane proteins. Platelet PCA, assessed by factor Xa (FXa) generation, was induced after activation and was inhibited by 48% and 76% with anti-TF and anti-FVIIa, respectively , but not by intrinsic pathway inhibi-tors. Platelets incorporated [ 35 S]-methi-onine into TF proteins with Mr of approximately 47 kDa, approximately 35 kDa, and approximately 60 kDa, more intensely after activation. Puromycin but not actinomycin D or DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) inhibited TF neosynthesis. Thus, human platelets not only assemble the clotting reactions on their membrane, but also supply their own TF for thrombin generation in a timely and spatially circum-scribed process. These observations simplify, unify, and provide a more coherent formulation of the current cell-based model of hemostasis. (Blood. 2007;109:5242-5250)

Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

“…Further, the possibility of manipulating platelet miRNAs expression and function as therapeutic tool can bear significant effects on specific protein levels and overall platelet reactivity. Furthermore, activated platelets induce tissue factor (TF) expression in human endothelial and smooth muscle cells, presumably by releasing soluble mediators such as serotonin and PDGF (72). Platelets also synthesise plasminogen activator inhibitor (PAI)-1, a main regulator of fibrinolysis (73).…”

No evidence for tissue factor on platelets

“…[2][3][4] Identification of these disease-causing mutations in patients can help in genetic testing to confirm or rule out a suspected syndrome or help determine a person's chance of developing or passing on a genetic disorder. Presently, more than 2796 mutations have been identified in BCPs.…”

Candida albicans effects the tissue factor activity of blood cells in Type II Diabetes Mellitus

“…As activated platelets release FVa, which is thought to be important in the initial phase of thrombin generation and in the feedback activation of FVII by FXa (18,19), this TF increase of platelets contaminated with C. albicans may reflect to the clot formation in type II DM patients. Ostreud revealed the persistence of controversy of the presence, synthesis and functional activity of TF in platelets (18) (20) claims the presence of TF in quiescent platelets and their enhanced activation. Furthermore, neo-synthesis of TF by platelets was reported in resting platelets as well as activated.…”