Mimuro J, Kimura S, Aoki N
J Clin Invest. 1986 Mar;77(3):1006-13. doi: 10.1172/JCI112352.
When blood coagulation takes place in the presence of calcium ions, alpha 2-plasmin inhibitor (alpha 2PI) is cross-linked to fibrin by activated coagulation Factor XIII (XIIIa) and thereby contributes to the resistance of fibrin to fibrinolysis. It was previously shown that the cross-linking reaction is a reversible one, since the alpha 2PI-fibrinogen cross-linked complex could be dissociated. In the present study we have shown that the alpha 2PI-fibrin cross-linking reaction is also a reversible reaction and alpha 2PI which had been cross-linked to fibrin can be released from fibrin by disrupting the equilibrium, resulting in a decrease of its resistance to fibrinolysis. When the fibrin clot formed from normal plasma in the presence of calcium ions was suspended in alpha 2PI-deficient plasma of buffered saline, alpha 2PI was gradually released from fibrin on incubation. When alpha 2PI was present in the suspending milieu, the release was decreased inversely to the concentrations of alpha 2PI in the suspending milieu. The release was accelerated by supplementing XIIIa or the presence of a high concentration of the NH2-terminal 12-residue peptide of alpha 2PI (N-peptide) which is cross-linked to fibrin in exchange for the release of alpha 2PI. When the release of alpha 2PI from fibrin was accelerated by XIIIa or N-peptide, the fibrin became less resistant to the fibrinolytic process, resulting in an acceleration of fibrinolysis which was proportional to the degree of the release of alpha 2PI. These results suggest the possibility that alpha 2PI could be released from fibrin in vivo by disrupting the equilibrium of the alpha 2PI-fibrin cross-linking reaction, and that the release would result in accelerated thrombolysis.
当血液在钙离子存在的情况下发生凝固时，α2 - 纤溶酶抑制剂（α2PI）通过活化的凝血因子 XIII（XIIIa）与纤维蛋白交联，从而增强纤维蛋白对纤维蛋白溶解的抵抗性。先前的研究表明，这种交联反应是可逆的，因为α2PI - 纤维蛋白原交联复合物可以解离。在本研究中，我们表明α2PI - 纤维蛋白交联反应也是可逆的，并且已与纤维蛋白交联的α2PI可以通过破坏平衡从纤维蛋白中释放出来，导致其对纤维蛋白溶解的抵抗性降低。当在钙离子存在下由正常血浆形成的纤维蛋白凝块悬浮于α2PI缺乏的血浆或缓冲盐溶液中时，孵育过程中α2PI会逐渐从纤维蛋白中释放出来。当悬浮介质中存在α2PI时，释放量会随着悬浮介质中α2PI浓度的增加而呈反比减少。补充 XIIIa 或存在高浓度的与纤维蛋白交联以换取α2PI释放的α2PI 的 NH2 - 末端 12 肽残基（N - 肽）会加速释放。当 XIIIa 或 N - 肽加速α2PI 从纤维蛋白中的释放时，纤维蛋白对纤维蛋白溶解过程的抵抗性降低，导致纤维蛋白溶解加速，且加速程度与α2PI 的释放程度成正比。这些结果表明，在体内可能通过破坏α2PI - 纤维蛋白交联反应的平衡从纤维蛋白中释放出α2PI，并且这种释放会导致血栓溶解加速。
