Le facteur tissulaire: Nouveaux concepts

In the traditional view, blood clotting is triggered when tissue factor (TF), a transmembrane glycoprotein which is expressed on the surface of a variety of extravascular cells, is exposed to blood after vessel injury. The binding of TF to its ligang factor VIIa FVIIa) activates the coagulation protease cascade, leading to thrombin generation and fibrin formation. In the past, a number of studies have reported the presence of plasma TF antigen of unclear significance; moreover, in 1999 Giesen et al reported that blood-borne TF accumulated in ex vivo thrombi. While the presence of functional TF in the blood of healthy subjects is still challenged, recent reports suggest that TF-expressing microparticles, originating from activated leucocytes, bind to the growing thrombi via an interaction between platelet P-selectin and P selectin glycoprotein ligand-1, its ligand on leucocytes. This form of intravascular TF is proposed to play a role in the thrombus development. Recent work has shown that TF has also characteristics of a true receptor. TF interaction with FVIIa not only induces clotting but also induces cell-signaling via activation of G-protein-coupled protease activated receptors (PARs). signaling pathways initiated by both protease activation of PARs (PAR-1 and PAR-2) and phosphorylation of the TF-cytoplasmic domain induce kinase activation and gene transcription. The TF-mediated activation of the expression of many genes points to its involvement in physio-pathological processes such as inflammation, metastasis, wound healing and atherosclerosis.