SYNTHESIS SECRETION COUPLING IN THE TYPE 11 PNEUMOCYTE

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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.