EXTRACELLULAR MATRIX AND TYPE II LUNG CELL METABOLISM

细胞外基质和 II 型肺细胞代谢

• 批准号: 3342774
• 负责人: D EUGENE RANNELS
• 金额: $ 9.23万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-30 至 1986-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3342774
• 关键词: alveolar macrophages; beta adrenergic agent; cell cell interaction; cell differentiation; connective tissue cells; connective tissue development; esterase; extracellular matrix; fibroblasts; gel electrophoresis; immunodiffusion; immunoelectrophoresis; lung; lung alveolus; lung disorder; organ culture; oxidizing agents; paraquat; phosphatidate phosphatase; phosphatidylcholines; pulmonary surfactants; respiratory enzyme; respiratory function; respiratory pharmacology; respiratory protein; respiratory toxin; secretion; thin layer chromatography; tissue /cell culture; transferase

The extracellular components of tissues, including the lung, have long been known to govern their physical-mechanical properties. Alterations in the content and/or organization of connective tissue elements is involved in both emphysema and pulmonary fibrosis. Recent reports of the influence of components of the matrix on cellular proliferations and differentiation have made it clear that the extracellular matrix, including collagens, glycosaminoglycans, and glycoproteins such as laminin and fibronectin, cannot be regarded as an inert scaffold. The goal of this project is to establish the metabolic consequences of Type II cell interaction with normal and oxidant-damaged extracellular matrix in a primary cell culture model. Type II cell proliferation is a significant component of pulmonary response to oxidant-induced damage, but the consequences of doubling the number of Type II cells in the lung and factors eliciting this proliferation are not known, nor are the metabolic responses of Type II cells to normal or damaged matrix understood. This project will investigate the responses of Type II granular pneumocytes in primary culture to a range of chemically-defined and biologically elaborated extracellular materials. Materials to be examined are collagen (Type I vs. Type IV) in different physical forms, laminin, fibronectin, extracellular matrix produced by fibroblasts and by endothelial cells and "biomatrix" isolated from whole lungs. Furthermore, the effect on Type II cell function of damage to matrix components and to matrix-producing cells by the oxidant paraquat will be examined. Type II functions to be monitored are a) synthesis and secretion of surfactant-associated proteins. Because pathways of protein metabolism are well defined, detailed analysis of the effects of environmental factors on specific steps of the process is possible, b) phosphotidylcholine secretion and its responsiveness to Beta-adrenergic agents, and c) activities of phosphatidic acid phosphohydrolase, cholinephosphate cytidylyl transferase, and non-specific esterases, all of which have been associated with the functional maturation of Type II cells. The mechanism by which Type II cell interaction with the extracellular environment modulates metabolism of surfactant-associated proteins will be explored in depth.

长期以来，包括肺在内的组织的细胞外成分一直是 已知可以控制其物理机械特性。 改变 结缔组织元素的内容和/或组织涉及 肺气肿和肺纤维化。 最近关于影响的报道 基质的组成部分在细胞增殖和分化 已经明确表明细胞外基质，包括胶原蛋白， 糖胺聚糖和糖蛋白，例如层粘连蛋白和纤连蛋白， 不能被视为惰性脚手架。 这个项目的目标是 建立与II型细胞相互作用的代谢后果 原代细胞培养中的正常和氧化剂受损的细胞外基质 模型。 II型细胞增殖是肺的重要组成部分 对氧化剂诱导的损害的反应，但增加了一倍的后果 肺中II型细胞的数量和引起此引起的因素 增殖尚不清楚，II型的代谢反应也不清楚 细胞达到正常或受损的基质。 这个项目将 研究原发性II型颗粒肺细胞的反应 培养到一系列化学定义和生物学上的培养 细胞外材料。 要检查的材料是胶原蛋白（I型VS。 IV型）以不同的物理形式，层粘连蛋白，纤连蛋白，细胞外 由成纤维细胞和内皮细胞和“ Biomatrix”产生的基质 与整个肺部分离。 此外，对II型细胞的影响 损伤对基质组件的损害和产生基质细胞的功能 将检查氧化剂。 II型功能要监视 是a）表面活性剂相关蛋白的合成和分泌。 因为 蛋白质代谢的途径是明确定义的，对 环境因素对过程特定步骤的影响是 b）磷酸苷胆碱的分泌及其对 β-肾上腺素能剂和c）磷脂酸的活性 磷酸水解酶，胆碱磷酸盐细胞苷转移酶和非特异性 酯酶，所有这些都与功能成熟有关 II型细胞。 II型细胞与 细胞外环境调节表面活性剂相关的代谢 将深入探索蛋白质。