PATHOBIOLOGY OF MACROPHAGE - FIBRONECTIN INTERACTIONS

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，并且是在 慢性炎症 无数亲密的互动发生 在这些细胞和凝血系统之间。 巨噬 结合凝血因子，促进凝血反应， 降解纤维蛋白，并结合血浆蛋白，但调节这些 交互. 一种这样的血浆蛋白是纤连蛋白，其具有 对包括纤维蛋白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 并增强某些巨噬细胞的吞噬活性， 这些细胞。 这一建议涉及的分子基础， 巨噬细胞-纤连蛋白相互作用，特别是细胞 负责结合该蛋白质的表面分子。 几 一系列证据表明，纤维连接蛋白的受体是 与其它细胞的不同（例如，成纤维细胞）和主要 研究的目的是确定这种受体， 单核吞噬细胞 三个独立但互补的 提出了一些方法，包括细胞的分级分离， 亲和层析，产生抗巨噬细胞 单克隆抗体，以及使用化学交联 试剂 受体的特性将在 详细使用这些方法结合吞噬体 隔离程序。 提出了实验来研究 这种细胞表面受体的特性，以确定其 与成纤维细胞受体的相关性，并在 单核细胞、巨噬细胞和细胞系。 这些实验有望提供新的见解， 纤连蛋白和单核吞噬细胞之间的相互作用， 为理解病理学中的这种相互作用提供了基础。 流程.

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.