PATHOBIOLOGY OF MACROPHAGE - FIBRONECTIN INTERACTIONS

巨噬细胞的病理学 - 纤连蛋白相互作用

• 批准号: 3291326
• 负责人: LIVINGSTON VAN DE WATER
• 金额: $ 10.69万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3291326
• 关键词: affinity chromatography; affinity labeling; atrophy; cell cell interaction; chemical binding; crosslink; cytoskeleton; extracellular matrix; fluorescence microscopy; gel electrophoresis; high voltage electrophoresis; human tissue; hybridomas; immunological substance; inflammation; ion exchange chromatography; macrophage; molecular biology; monoclonal antibody; monocyte; phagocytes; phagocytosis; radiotracer; thin layer chromatography

Mononuclear phagocytes play an important role in many pathological processes involving fibrin, and are ubiquitous cells in chronic inflammation. Numerous and intimate interactions occur between these cells and the coagulation system. Macrophages bind coagulation factors, promote clotting reactions, bind and degrade fibrin, and bind plasma proteins though to modulate these interactions. One such plasma protein is fibronectin which has discrete binding sites that are specific for ligands including fibrin, Factor XIIIa and cells. This adhesive glycoprotein is synthesized by marcophages and also enhances certain phagocytic activities of these cells. This proposal is concerned with the molecular basis for macrophage-fibronectin interactions, and particularly the cell surface molecule(s) responsible for binding this protein. Several lines of evidence suggest that the receptor for fibronectin is different than that of other cells (e.g., fibroblasts) and the major aim of research proposed is to identify this receptor in mononuclear phagocytes. Three independent but complementary approaches are proposed, including the fractionation of cells by affinity chromatography, the generation of anti-macrophage monoclonal antibodies, and the use of chemical cross-linking reagents. The properties of the receptor will be examined in detail using these methods in conjunction with phagosome isolation procedures. Experiments are proposed to study the properties of this cell surface receptor, to determine its relatedness to the fibroblast receptor, and to study it in monocytes, macrophages and cell lines. These experiments are expected to provide new insights into interactions between fibronectin and mononuclear phagocytes and provide a basis for understanding this interaction in pathological processes.

单核巨噬细胞在许多疾病中起着重要作用 涉及纤维蛋白的病理过程，是普遍存在的 慢性炎症。发生了无数亲密的互动 在这些细胞和凝血系统之间。巨噬细胞 结合凝血因子，促进凝血反应，结合和 降解纤维蛋白，并结合血浆蛋白来调节这些 互动。一种这样的血浆蛋白是纤维连接蛋白，它具有 对包括纤维蛋白在内的配体具有特异性的离散结合位点， 因子XIIIA和细胞。这种粘附性糖蛋白是由 还能增强某些吞噬细胞的吞噬活性 这些细胞。 这项提议涉及到的分子基础 巨噬细胞-纤维连接蛋白的相互作用，特别是细胞 负责结合这种蛋白质的表面分子(S)。几个 一系列证据表明，纤维连接蛋白的受体是 不同于其他细胞(如成纤维细胞)和主要 所提出的研究目的是确定这种受体在 单核巨噬细胞。三个独立但相辅相成 提出了一些方法，包括通过以下方式对细胞进行分级 亲和层析，产生抗巨噬细胞 单抗和化学交联剂的使用 试剂。该受体的特性将在 结合吞噬小体使用这些方法的细节 隔离程序。建议进行实验，以研究 这种细胞表面受体的性质，以确定其 与成纤维细胞受体的相关性，并对其进行研究 单核细胞、巨噬细胞和细胞系。 这些实验有望提供新的见解 纤维连接蛋白与单核巨噬细胞的相互作用及机制 为在病理学上理解这种相互作用提供了基础 流程。