PLATELET-FIBRINOGEN INTERACTIONS

纤维蛋白原在血小板聚集中起着至关重要的作用。 在血小板激活后，纤维蛋白原与一种钙- 血小板膜糖蛋白依赖复合体(GP)IIb 还有伊拉。有人提出，纤维蛋白原与一种二聚体 结构和双重对称性，可以作为沟通的桥梁 相邻血小板中存在两个GP IIb-IIIa复合体。至少两口井- 纤维蛋白原中定义的序列，N- γ链末端和Arg-Gly-Asp序列 A阿尔法链(A阿尔法95-97和/或A阿尔法574-576)是 显示与血小板GP IIb-IIIa相互作用。我们最近做了 表明合成肽Bβ15-42源于氨基 Bβ链末端，抑制ADP和凝血酶诱导 血小板聚集呈剂量依赖关系。此外， 在结合研究中，该肽抑制125I-纤维蛋白原与 激活的血小板。这种多肽是由体内的 凝血酶和纤溶酶对纤维蛋白原和HAS的联合作用 在外周血液中检测到。这项提议的目的是 为了进一步定义所需的最小氨基酸序列 这种效应，以确定这种多肽的作用是否 通过与GP IIb-IIIa或与 纤维蛋白原，并确定该肽对血管内皮功能的影响。 其他粘附性糖蛋白与GP IIb-IIIa的相互作用在……里面 此外，缺乏Bβ15-42的纤维蛋白原将通过 乌鸦蛇毒中蛋白酶III的裂解作用 这种纤维蛋白原对血小板聚集的影响将是 下定决心。这些研究将阐明 血小板纤维蛋白原中Bβ链的氨基末端 互动。

Fibrinogen plays an essential role in platelet aggregation. Following platelet activation, fibrinogen binds to a calcium- dependent complex of platelet membrane glycoproteins (Gp) IIb and IIIa. It has been proposed that fibrinogen, with a dimeric structure and two-fold symmetry, may act as a bridge between two Gp IIb-IIIa complex in adjacent platelets. At least two well- defined sequences in fibrinogen, the gamma-400-411 in the N- terminal part of gamma chain and the Arg-Gly-Asp sequences in the A alpha chain (A alpha 95-97 and/or A alpha 574-576) are shown to interact with platelet Gp IIb-IIIa. We have recently shown that the synthetic peptide B beta 15-42 derived from amino terminal end of B beta chain, inhibits ADP and thrombin-induced platelet aggregation in a dose-dependent manner. Furthermore, in binding studies this peptide inhibits 125I-fibrinogen binding to activated platelets. This peptide is generated in vivo by the combined actions of thrombin and plasmin on fibrin(ogen) and has been detected in peripheral blood. The aims of this proposal are to further define the minimal aminoacid sequence required for this effect, to determine whether the effect of this peptide is mediated through its interaction with Gp IIb-IIIa or with fibrinogen, and to determine the effect of this peptide on the interaction of other adhesive glycoproteins to Gp IIb-IIIa. In addition, fibrinogen lacking B beta 15-42 will be prepared by cleavage with Protease III from Crotalus atrox venom and the effect of this fibrinogen on platelet aggregation will be determined. These studies will elucidate the importance of aminoterminal end of B beta chain in platelet-fibrinogen interactions.