ALVEOLAR HOMEOSTASIS OF SURFACTANT LIPIDS AND PROTEINS

表面活性剂脂质和蛋白质的肺泡稳态

• 批准号: 6606075
• 负责人: ALAN H JOBE
• 金额: $ 28.23万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6606075
• 关键词: adduct; alveolar macrophages; confocal scanning microscopy; genetically modified animals; intermolecular interaction; intracellular transport; laboratory mouse; molecular assembly /self assembly; phosphatidylcholines; phospholipids; protein degradation; protein structure function; protein transport; pulmonary surfactants; respiratory epithelium

Our hypothesis is that the surface proteins interact with the phospholipids and participate in the regulation of surfactant homeostasis. The goals of this project are to characterize the normal forms assumed by the lipid and protein components of surfactant from secretion by type II cells to alveolar clearance, recycling and catabolism. Normal radiolabeled lipid and protein components of surfactant will be used to identify the forms taken in the airspace by which component in vivo. Parallel experiments will be used to study how the surfactant components move through the form conversions of surfactant in vitro. The importance to and effects of the surfactant protein components SP-A, SP-B, and SP-C on surfactant form conversions in vitro and surfactant function will be evaluated using transgenic mice that are deficient or have abnormal levels of expression of the surfactant proteins. Surfactant component clearance from the airspaces, and recycling and/or catabolism will be quantified using an analog of dipalmitoylphosphatidylcholine and surfactant proteins with residualizing carbohydrate adducts that are not catabolized. The relative importance of type II cells, Clara cells and macrophages to surfactant homeostasis will be quantified, and subcellular organelles important to surfactant component trafficking will be identified using confocal microscopy. Understanding normal surfactant homeostasis will permit new insights into lung dysfunction with injury.

我们的假设是表面蛋白与磷脂相互作用并参与表面活性剂稳态的调节。该项目的目标是表征表面活性剂的脂质和蛋白质成分从 II 型细胞分泌到肺泡清除、再循环和分解代谢的正常形式。表面活性剂的正常放射性标记脂质和蛋白质成分将用于识别哪种成分在体内采取的形式。平行实验将用于研究表面活性剂成分如何在体外通过表面活性剂的形态转换进行移动。表面活性剂蛋白组分 SP-A、SP-B 和 SP-C 对表面活性剂体外形式转化和表面活性剂功能的重要性和影响将使用表面活性剂蛋白表达缺陷或异常水平的转基因小鼠进行评估。将使用二棕榈酰磷脂酰胆碱的类似物和表面活性剂蛋白以及未分解代谢的残留碳水化合物加合物来量化表面活性剂成分从空域的清除以及再循环和/或分解代谢。 II 型细胞、Clara 细胞和巨噬细胞对表面活性剂稳态的相对重要性将被量化，并且对表面活性剂成分运输重要的亚细胞细胞器将使用共聚焦显微镜进行鉴定。了解正常的表面活性剂稳态将使我们对损伤引起的肺功能障碍有新的认识。