SYNTHESIS SECRETION COUPLING IN THE TYPE 11 PNEUMOCYTE

作为肺表面活性物质的来源，II型肺泡上皮细胞 在正常肺功能和肺结核的病理生理学中起着关键作用。 一些疾病的状态。 本研究计划的目的是 更好地了解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及其整合 生物合成 细胞膜受体（肾上腺素能，胆碱能， 将使用II型肺细胞的胰岛素）来研究外源性 刺激。 受体结合的结果，无论是在局部 膜特性（膜电位，磷脂甲基化， 磷脂酰肌醇周转）以及对产生 将评估细胞内介质（环核苷酸，Ca++）。 的 研究中的信息将用于确定这些措施的影响。 肺表面活性剂磷脂的生物合成过程， 特别是二棕榈酰磷脂酰胆碱和磷脂酰甘油。 将使用纯化的II型细胞进行研究，并分离 亚细胞组分，以研究细胞内介质的作用 在对磷脂的特定酶的分泌反应过程中产生 合成. 这些研究将确定分子和过程 参与II型肺细胞细胞功能的整合 及其与其他分泌上皮的关系。

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.