In thrombosis, vessel wall injury exposes subendothelial tissue factor (TF) and releases intracellular nucleic acids to initiate coagulation through the extrinsic (TF-FVIIa) and intrinsic (FXIIa, FXIa and FIXa) pathways, respectively. Subendothelial collagen binds von Willebrand factor (vWF), which promotes platelet adhesion and activation through the glycoprotein Ibα (GPIbα). Damaged endothelial cells and platelets provide the initial prothrombotic surface for the generation of thrombin by the prothrombinase (FVa-FXa) complex. Thrombin converts fibrinogen to fibrin and triggers platelets to expose P-selectin on the platelet surface and activate the integrin aIIbβ3 that binds fibrinogen or fibrin. The recruitment of leukocytes is supported by platelet-leukocyte interactions involving counterligands PSGL-1–P-selectin, integrin αMβ2-GPIbα or αMβ2-fibrin-αIIbβ3. Neutrophils are stimulated by platelet granule contents to exteriorize nucleosomes and release neutrophil proteases, including elastase (NE). Circulating, endothelial cell–derived or platelet-derived TFPI inhibits further thrombin generation. Massberg et al.4 show that TFPI-α binds neutrophil-derived nucleosomes, resulting in neutrophil elastase–mediated TFPI degradation and enhanced thrombus formation, even in large blood vessels. Myeloid cell–derived microparticles carry blood-borne tissue factor that is recruited through a PSGL-1–P-selectin pathway to growing thrombi, providing a possible target for circulating TFPI-α and the thrombosis-promoting effects of neutrophil-derived proteases.
其他凝血機轉的圖片，可以參考這邊：
留言列表
醫藥類 (14)
