The roles of fibrinogen and fibrin in hemostasis and thrombosis.
The roles of fibrinogen and fibrin in hemostasis and thrombosis.
复制标题
作者：
M. Mosesson
纤维蛋白原蛋白水解转化为纤维蛋白导致自组装形成凝块基质，随后通过 fXIIIa 交联形成体内血栓的主要结构元件。纤维蛋白的形成和组装产生了调节凝血、交联和纤维蛋白溶解的速率和程度的新特性。这些是由纤维蛋白 (1) 在非底物位点结合凝血酶的能力引起的，从而限制了其扩散性，但同时保留了其催化潜力； (2) 结合fXIII，调节其对fXIIIa的激活，并在纤维蛋白交联发生后限制fXIII的进一步激活； (3)结合α2-PI、t-PA和纤溶酶原并调节纤维蛋白溶解的起始和传播。纤维蛋白原和纤维蛋白含有几个潜在的血小板结合位点，可与血小板 GPIIb/IIIa 受体相互作用，从而促进它们参与止血过程。另外，这里没有详细介绍的不太明确的相互作用，例如纤维蛋白原或纤维蛋白与其他血浆蛋白、细胞或组织基质成分之间的相互作用，表明了其他功能，这些功能与上面详述的那些功能一起，将进一步定义其在调节止血、炎症和伤口愈合过程中的多种作用。
Proteolytic conversion of fibrinogen to fibrin results in self-assembly to form a clot matrix that subsequently becomes cross-linked by fXIIIa to form the main structural element of the thrombus in vivo. Fibrin formation and assembly lead to new properties that regulate the rate and extent of clotting, cross-linking, and fibrinolysis. These are brought about by the ability of fibrin (1) to bind thrombin at a nonsubstrate site, thus limiting its diffusability but at the same time preserving its catalytic potential; (2) to bind fXIII, regulate its activation to fXIIIa, and limit further activation of fXIII once fibrin cross-linking has occurred; and (3) to bind alpha 2-PI, t-PA, and plasminogen and regulate the initiation and propagation of fibrinolysis. Fibrinogen and fibrin contain several potential platelet binding sites that interact with platelet GPIIb/IIIa receptors, and thus promote their participation in the hemostatic process. Additional, less well-defined interactions, not covered in detail here, such as those between fibrinogen or fibrin and other plasma proteins, cells, or tissue matrix components, suggest other functions that, along with those detailed above, will further define its multiple roles in modulating hemostasis, inflammation, and the wound healing process.