TISSUE INJURY AND REPAIR--FIBRONECTIN AND MACROPHAGES

该计划项目申请代表了一个 具有凝聚力但多学科的调查小组，以确定角色 纤维连接蛋白在与病理生理直接相关的过程中的作用 损伤和败血症的后遗症。基础和临床研究都有 支持纤维连接蛋白在这些疾病中起重要作用的概念 回应。这些目标将通过以下方面的协调努力实现 核心和五个科学项目。五个方面的总体目标 科学项目是1)定义和描述 纤维连接蛋白及其受体在纤维蛋白结合和降解中的作用 通过单核巨噬细胞。这些研究将描述这些过程 通过体外和实验性脓毒症内的机械性方法 体内血栓状态。2)确立粘合剂的作用 糖蛋白与细胞受体相互作用的研究进展 血小板和白细胞。这种结合在血小板诱导中的作用 白细胞功能的改变也将被讨论。3)评估 组织损伤产物进入血管间室和 纤维连接蛋白及其受体在血管中的作用 清除和降解。研究将集中在胶原蛋白和肌动蛋白以及 将在烧伤的情况下在体内完成，并在体外完成 分离的肝细胞。4)评估遵守《公约》的影响 单核巨噬细胞对内皮源性基质和单个基质的作用 蛋白质对单核细胞功能活性和炎症的影响 巨噬细胞。这些体外研究的重点将放在 单核细胞吞噬功能的自分泌调控 花生四烯酸和单因子。5)对机制的评价 纤维连接蛋白被结合到内皮下基质中。本研究 我将检验这样一种假设，即这一过程受制于 纤维连接蛋白合成速率与纤维连接蛋白分泌极化 和纤维连接蛋白受体连接到基底表面。科学部门 将由负责计划的核心提供支持 给药、制备单核巨噬细胞、制备剂 生物化学、形态学、免疫细胞化学和提供统计学 服务。这一总体努力将提供以下方面的重要基本信息 纤维连接蛋白和单核吞噬细胞的作用最终可能 加强对伤者的了解和治疗方法 有耐心的。

This program project application represents the combined efforts of a cohesive yet multidisciplinary group of investigators to delineate the role of fibronectin in processes directly relevant to the pathophysiological sequelae to injury and sepsis. Both basic and clinical studies have supported the concept that fibronectin serves an important role in these responses. The aims will be achieved through the coordinated efforts of a Core and five scientific projects. The overall objectives of the five scientific projects are 1) To define and characterize the role of fibronectin and fibronectin receptors in binding and degradation of fibrin by mononuclear phagocytes. These studies will characterize these processes via mechanistic approaches in vitro and within experimental septic and thrombotic states in vivo. 2) To establish the role of adhesive glycoproteins and cellular receptors in supporting the interaction of platelets and leukocytes. The role of such binding in platelet-induced modification of leukocyte functions will also be addressed. 3) To assess the entrance of products of tissue injury into the vascular compartment and the role of fibronectin and fibronectin receptors in their vascular clearance and degradation. Studies will focus upon collagen and actin and will be completed in vivo in the context of burn injury and in vitro with isolated hepatic cells. 4) To assess the influence of the adherence of mononuclear phagocytes to endothelial derived matrix and individual matrix proteins on the functional activity of monocytes and inflammatory macrophages. Emphasis in these in vitro studies will be placed upon autocrine control of mononuclear phagocyte function via metabolites of arachidonic acid and monokines. 5) Evaluation of the mechanism by which fibronectin is incorporated into the subendothelial matrix. This study will examine the hypothesis that this process is subserved by regulation of the rate of fibronectin synthesis and polarization of fibronectin secretion and fibronectin receptors to the basal surface. The scientific sections will be supported by a Core which has responsibility for program administration, preparation of mononuclear phagocytes, preparative biochemistry, morphology, immunocytochemistry, and provision of statistical services. This overall effort will provide important basic information on the role of fibronectin and mononuclear phagocytes which may ultimately enhance the understanding of and therapeutic approaches to the injured patient.