This is an application for interdisciplinary studies of Development, Control, and Disorders of Pulmonary Alveolar Stability. The purposes of this proposal 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; 3) to characterize the biochemical 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 govern secretion and re-uptake of surfactant components in intact animals; 6) to determine the role of glucocorticoid and thyroid hormones in differentiation of the fetal lung; and 7) to find optimal methods of treating infants with severe respiratory distress, especially in the management of artificial ventilation.
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