ALVEOLAR HOMEOSTASIS OF SURFACTANT LIPIDS AND PROTEINS

我们的假设是，表面蛋白与磷脂相互作用，并参与调节表面活性剂的稳态。本项目的目标是表征表面活性剂的脂质和蛋白质组分从II型细胞分泌到肺泡清除、再循环和catalysts的正常形式。将使用表面活性剂的正常放射性标记脂质和蛋白质组分来鉴定在体内由哪种组分在空气空间中采取的形式。平行实验将被用来研究表面活性剂组分如何在体外通过表面活性剂的形式转化而移动。将使用缺乏表面活性蛋白或表面活性蛋白表达水平异常的转基因小鼠评价表面活性蛋白组分SP-A、SP-B和SP-C对体外表面活性剂形式转化和表面活性剂功能的重要性和影响。将使用二棕榈酰磷脂酰胆碱和表面活性剂蛋白质的类似物与未分解代谢的残留碳水化合物加合物定量表面活性剂组分从空气空间的清除以及再循环和/或分解。II型细胞，克拉拉细胞和巨噬细胞的相对重要性，表面活性剂的稳态将被量化，和亚细胞器的表面活性剂组分运输的重要性将被确定使用共聚焦显微镜。了解正常的表面活性物质稳态将允许新的见解肺损伤功能障碍。

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.