CELLULAR INTERACTIONS OF PLASMA PROTEINS

该计划项目将存在于Sol Sherry血栓形成 研究中心，致力于提高我们的理解， 动脉粥样硬化的病因、发病机制、诊断和治疗 静脉血栓形成和出血性疾病。 的研究活动 该计划分为项目，统一在 检查各种血浆蛋白与 血小板、内皮细胞和白细胞受体参与了细胞凋亡的调控。 止血的生理和病理过程， 血栓形成和各种酶活性的调节 丝氨酸蛋白酶 项目1（P.N.沃尔什，血小板受体介导 X因子激活）的重点是膜的机制， 组装F-X活化复合物，目的是实现 蛋白质的完整结构和功能表征- 受体相互作用参与组装的F-X激活 血小板表面的复合物。 项目2（R.W.科尔曼， 激肽原的抗粘附和抗凝血活性）将探测 血浆高分子量激肽原（HK）与 包括血小板、嗜中性粒细胞和单核细胞的血细胞以及 内皮细胞 与HK相互作用的各种域 将表征细胞和蛋白质配体。 项目3（南卡罗来纳州） 丝氨酸蛋白酶抑制剂结构与抗中性粒细胞的发展 丝氨酸蛋白酶抑制剂）将专注于结构-活性关系， 天然存在的抗凝剂丝氨酸蛋白酶抑制剂，抗凝血酶III，并将目标 开发靶向血管壁的重组丝氨酸蛋白酶抑制剂， 局部阻断凝血酶和弹性蛋白酶的作用。 核心A（P.N. 沃尔什，行政核心）将提供财政监督和文书 支持. 核心B（J.D. Lambris，蛋白质化学和分子 建模核心实验室）将提供技术支持， 分子建模和合理的合成肽设计建议 和合成。 所有的调查人员都有合作计划 与其他项目负责人进行研究，并与 并与其他项目共享智力和物质资源 领导人的人选信号 从这些研究中获得的信息将有可能 合理开发旨在治疗 出血综合征或抑制或预防血栓形成 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.