SYNTHESIS SECRETION COUPLING IN THE TYPE 11 PNEUMOCYTE

肺泡II型上皮细胞作为肺表面活性物质的来源 在正常的肺功能和慢性阻塞性肺疾病的病理生理学中起着关键作用。 一些疾病状态。这项研究提案的目的是 更好地理解II型细胞内的调节，特别是 激素刺激的肺表面活性物质分泌与其整合 生物合成。 细胞膜受体(肾上腺素能、胆碱能、 I型肺泡细胞的胰岛素)将用于研究外源激素的作用 刺激物。激素-受体结合对局限化的影响 膜特性(膜电位、磷脂甲基化、 磷脂酰肌醇周转率)以及 将对细胞内介质(环核苷酸、钙离子)进行评估。这个 这些研究的信息将被用来确定这些措施的影响 肺表面活性物质磷脂生物合成研究进展， 特别是二棕榈酰磷脂酰胆碱和磷脂酰甘油。 研究将使用纯化的II型细胞和分离的 亚细胞组份研究细胞内介质的作用 在对磷脂特定酶的分泌反应中产生 综合。这些研究将确定分子和过程 参与了II型肺泡细胞细胞功能的整合 以及它与其他分泌上皮细胞的关系。

As the source of pulmonary surfactant, the type II alveolar epithelial cell plays a critical role in normal lung function and in the pathophysiology of a number of disease states. The objective of this research proposal is to better understand the regulation within the type II cell, specifically, the integration of hormonally stimulated pulmonary surfactant secretion and its biosynthesis. Specific assays for cell membrane receptors (adrenergic, cholinergic, insulin) of type II pneumocytes will be used to study effects of exogenous stimuli. The consequences of hormone-receptor binding both on localized membrane properties (membrane potential, phospholipid methylation, phosphatidylinositol turnover) as well as on the generation of intracellular mediators (cyclic nucleotides, Ca++) will be assessed. The information from the studies will be used to determine the effects of these processes on the biosynthesis of pulmonary surfactant phospholipids, particularly dipalmitoylphosphatidylcholine and phosphatidylglycerol. Studies will be performed using purified type II cells and isolated subcellular fractions to investigate the effects of intracellular mediators generated during the secretory response on specific enzymes of phospholipid synthesis. These studies will determine the molecules and processes involved in the integration of cellular functions of the type II pneumocyte and its relationship to other secretory epithelia.