CELLULAR INTERACTIONS OF PLASMA PROTEINS

该计划项目将存在于Sol Sherry血栓症中 研究中心，致力于增进我们对 动脉粥样硬化性心脏病的病因、发病机制、诊断和治疗 静脉血栓形成和出血性疾病。研究活动 被划分为项目，这些项目在 不同血浆蛋白与蛋白质相互作用的研究 血小板内皮细胞和白细胞受体参与血管内皮细胞损伤 止血和止血的生理和病理过程 血栓形成与多种酶活性的调节 丝氨酸蛋白酶。项目1(P.N.Walsh，血小板受体介导 凝血因子-X激活)侧重于膜的机制 F-X活化复合体的组装，目的是实现 蛋白质的完整结构和功能表征- F-X激活组装过程中的受体相互作用 血小板表面的复合体。项目2(R.W.科尔曼， 激肽原的抗粘附性和抗凝血活性)将探讨 血浆高分子激肽原(HK)与血管活性物质的相互作用 包括血小板、中性粒细胞和单核细胞在内的血细胞以及 内皮细胞。与香港有互动的域名 将对细胞和蛋白质配体进行表征。项目3(S.C. Bock、Serpin结构与抗中性粒细胞的发展 Serpins)将重点放在结构-活性关系上 天然抗凝丝氨酸，抗凝血酶III，并将目标 研制以血管壁为靶点的重组蛇毒 局部阻断凝血酶和弹力酶的作用。核心A(P.N. 沃尔什，行政核心)将提供财政监督和文书工作 支持。核心B(J.D.兰布里斯，蛋白质化学和分子 建模核心实验室)将提供技术支持和 关于分子建模和合理合成肽设计的建议 和综合体。所有的调查人员都有合作的计划 与其他项目负责人进行研究，并将与 并与其他项目共享智力和体力资源 领袖们。从这些研究中获得的信息将使 合理发展旨在治疗的治疗干预措施 出血性综合征或抑制或防止血栓形成 血管。

This Program Project will exist within the Sol Sherry Thrombosis Research Center which is dedicated to advancing our understanding of the etiology, pathogenesis, diagnosis and treatment of arterial and venous thrombosis and hemorrhagic diseases. The research activities of the Program are divided into projects that are unified in the examination of the interactions between various plasma proteins with platelet endothelial cell and leukocyte receptors involved int he physiological and pathological processes of hemostasis and thrombogenesis and the regulation of the enzymatic activity of various serine proteases. Project 1 (P.N. Walsh, Platelet Receptor-Mediated Factor-X Activation) focuses on the mechanisms of membrane assembly of the F-X activating complex and aims to accomplish a complete structural and functional characterization of the protein- receptor interactions involved in the assembly of the F-X activating complex on the platelet surface. Project 2 (R.W. Colman, Antiadhesive and Anticoagulant Activity of Kininogens) will probe the interactions of plasma high molecular weight kininogen (HK) with blood cells including platelets, neutrophils and monocytes as well as endothelial cells. The domains with HK that interact with various cellular and protein ligands will be characterized. Project 3 (S.C. bock, Serpin Structure and the Development of Neutrophil-Resistant Serpins) will focus on the structure-activity relationships with a naturally occurring anticoagulant serpin, antithrombin III, and will aim to develop recombinant serpins which are targeted tot he vessel wall to block the actions of thrombin and elastase locally. Core A (P.N. Walsh, Administrative Core) will provide fiscal oversight and clerical support. Core B (J.D. Lambris, Protein chemistry and Molecular Modeling Core Laboratory) will provide both technical support and advice on molecular modeling and rational synthetic peptide design and synthesis. All the investigators have plans for collaborative research with each of the other project leaders and will consult with and share intellectual and physical resources with the other project leaders. The information gained from these studies will make possible the rational development of therapeutic interventions designed to treat hemorrhagic syndromes or to inhibit or prevent thrombogenesis in blood vessels.