Francis C W, Bunce L A, Sporn L A
Department of Medicine, University of Rochester School of Medicine & Dentistry, New York.
Blood Cells. 1993;19(2):291-306; discussion 306-7.
Endothelial cells (EC) interact with fibrin at sites of vascular injury, thrombosis, inflammation and tumor growth, whereas they are quiescent when exposed to circulating fibrinogen. To determine the structural basis for specific interaction with fibrin we have characterized the response of EC to fibrin of varying structure. Fibrin was prepared with thrombin, which cleaves both fibrinopeptide A (FPA) and fibrinopeptide B (FPB), with Reptilase, which cleaves only FPA, and with contortrix procoagulant to cleave only FPB. Fibrin with FPB cleavage stimulated release of von Willebrand factor from EC Weibel-Palade bodies and also supported cell spreading. Involvement of the amino terminus of the fibrin beta chain in the response was shown by stimulation of von Willebrand factor release by the peptide beta 15-42. Also, fibrin prepared from a fibrinogen derivative lacking residues 15-42 of the beta chain failed to support EC spreading. EC adhesion was unaffected by the pattern of fibrinopeptide cleavage or by the removal of peptide beta 15-42 from fibrin. The results indicate that separate sites on the fibrin molecule mediate adhesion and spreading, and that the latter requires cleavage of FPB and the new amino terminus of the beta chain. They further suggest that cellular responses to fibrin are regulated by the proteolytic cleavages and conformational changes that convert fibrinogen to fibrin and may also be modulated by plasmic or elastase degradation.
内皮细胞（EC）在血管损伤、血栓形成、炎症和肿瘤生长部位与纤维蛋白相互作用，而当暴露于循环纤维蛋白原时它们处于静止状态。为了确定与纤维蛋白特异性相互作用的结构基础，我们已对EC对不同结构纤维蛋白的反应进行了表征。用凝血酶制备纤维蛋白，凝血酶可切割纤维蛋白肽A（FPA）和纤维蛋白肽B（FPB）；用蛇毒凝血酶制备纤维蛋白，蛇毒凝血酶仅切割FPA；用矛头蝮蛇促凝剂制备纤维蛋白，矛头蝮蛇促凝剂仅切割FPB。切割FPB的纤维蛋白刺激了EC韦贝尔-帕拉德小体中血管性血友病因子的释放，并且还支持细胞铺展。纤维蛋白β链氨基末端参与该反应通过肽β15-42刺激血管性血友病因子释放得以证明。同样，由缺乏β链15-42位残基的纤维蛋白原衍生物制备的纤维蛋白不能支持EC铺展。EC黏附不受纤维蛋白肽切割模式或从纤维蛋白中去除肽β15-42的影响。结果表明，纤维蛋白分子上不同的位点介导黏附和铺展，并且后者需要切割FPB和β链的新氨基末端。它们进一步表明，细胞对纤维蛋白的反应受将纤维蛋白原转化为纤维蛋白的蛋白水解切割和构象变化调节，并且也可能受血浆或弹性蛋白酶降解的调节。
