THE SURFACE PROTEINS OF THE PULMONARY ENDOTHELIAL CELL

肺内皮细胞的表面蛋白

• 批准号: 3087168
• 负责人: PETER M LUCKETT
• 金额: $ 7.65万
• 依托单位: LOS ANGELES COUNTY HARBOR-UCLA MED CTR
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1989-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3087168
• 关键词: antibody formation; aorta; biological models; capillary; child (0-11); electron microscopy; gel electrophoresis; human subject; hyperoxia; immunoprecipitation; lung disorder; membrane proteins; microcirculation; model design /development; monoclonal antibody; newborn animals; newborn human (0-6 weeks); phase contrast microscopy; radiotracer; reagent /indicator; respiratory function; sheep; tissue /cell culture; trauma; vascular endothelium

The surface proteins of the pulmonary endothelial cell are responsible for the metabolic activities which colllectively are known as the metabolic functions of the lung. The endothelium also participates in the inflammatory response. Changes in surface function during injury suggest a modulation of surface proteins. I hypothesize that endothelia respond to injury with shifts in function which are programmed to initiate and amplify inflammation. These changes in function will be reflected in the selective loss of surface proteins and the expression of new surface proteins. It is the purpose of this research to study the modulation of endothelial surface proteins in injury by examining these proteins in endothelia grown under different conditions. In phase I of this proposal I will 1) develop a highly differentiated model of the pulmonary microvascular endothelium applying existing expertise, 2) examine the surface membrane proteins of aortic, pulmonary arteriolar, venular, and capillary endothelia grown in culture and for comparison the proteins of aortic endothelia harvested but not cultured, 3) look for changes in surface proteins of endothelia during injury in an hyperoxic environment, 4) and develop antibodies (monoclonal and polyclonal) to proteins which are either lost or induced in injury. In phase II of this proposal, information concerning the time course of protein shifts and the immunoreagents developed from phase I will be applied to the study of microvascular injury in a chronically instrumented sheep model of hyperoxic lung injury. These studies will lead to a better understanding of the endothelium's role in the evolution of microvascular injury and will eventually allow me to search for the appearance of proteins in the plasma of critically ill patients which may serve as early indicators of acute lung injury.

肺内皮细胞的表面蛋白负责 代谢活动被称为代谢 肺的功能。 内皮也参与 炎症反应。 受伤期间表面功能的变化表明 表面蛋白的调节。 我假设内皮回应 受伤随功能转移而启动和扩增的功能变化 炎。 这些功能的变化将反映在选择性 表面蛋白的丧失和新表面蛋白的表达。 这是 这项研究的目的是研究内皮表面的调节 通过在生长的内皮中检查这些蛋白质的损伤蛋白质 不同的条件。 在该提案的第一阶段，我将1）开发一个高度差异化的模型 使用现有专业知识的肺微血管内皮，2） 检查主动脉，肺动脉的表面膜蛋白， 静脉和毛细血管内皮在培养物中生长，为了进行比较 收获但未培养的主动脉内皮的蛋白质，3）寻找 在高氧化中受伤期间内皮表面蛋白的变化 环境，4）并发展为抗体（单克隆和多克隆） 损失或诱发受伤的蛋白质。 在该提案的第二阶段，有关时间课程的信息 蛋白质转移和从第一阶段开发的免疫反应将是 应用于长期仪器中微血管损伤的研究 高氧肺损伤的绵羊模型。 这些研究将导致更好 了解内皮在微血管演变中的作用 受伤，最终将使我可以寻找 重病患者血浆中的蛋白质可能会尽早 急性肺损伤的指标。