This application proposes to continue multidisciplinary studies of Development, Control, and Disorders of Pulmonary Alveolar Stability. The purposes are 1) to identify and characterize the cellular mechanisms that participate in the synthesis, secretion, and clearance of lung surfactant in the normal lung; 2) to study the relationships between composition and physicochemical properties of lung surfactant, especially its apoproteins and their role in surfactant metabolism; 4) to isolate and study alveolar epithelial cells with special regard to mechanisms of secretion and secretory products and to factors that control the cells' differentiation; 5) to elucidate the most important factors that control secretion and re-uptake of surfactant components in isolated cells and in intact animals; and 6) to determine the role of glucocorticoid and thyroid hormones in differentiation of the fetal lung. The overall purpose of these investigations is to deepen our understanding of the normal processes of alveolar stabilization and to contribute to the development of new concepts and methods for the treatment of diseases, such as respiratory distress syndromes, that destroy alveolar stability.
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