DEVELOPMENT AND CONTROL OF PULMONARY ALVEOLAR STABILITY

本申请建议继续多学科研究

This application proposes to continue multidisciplinary studies of development, control and disorders of pulmonary alveolar stability. Disordered alveolar stability is the primary problem in respiratory distress syndrome of the newborn and contributes significantly to the pathophysiology of other common forms of lung disease including adult respiratory distress syndrome and pneumonia. The proposal focuses on two related determinants of alveolar stability. The first is the function, structure, and metabolism of surfactant: a secretion of type II alveolar epithelial cells. The second is the regulation of alveolar epithelial cell phenotype. The goals are :- l. to study the regulation of cholesterol metabolism in type II cells and the trafficking of plasma lipoproteins in the lung with a particular emphasis on the role of endocytotic lipoprotein receptors, 2. to investigate the co-ordinate regulation of endocytosis and exocytosis in type II cells and to examine the role of plasma lipoprotein receptors and specific signalling pathways in these events, 3. to determine the importance of specific structural elements in the surfactant apoproteins in the metabolism of surfactant lipoproteins, 4. to examine molecular mechanisms, physiological manifestations and theoretical models of surface phenomena in lung function, 5. to determine the effects of physical stimuli, particularly distension, on the growth and maturation of the alveolar region of the lung. 6. to characterize phenotypic markers of alveolar epithelial cells and using these markers study the development and regulation of epithelial cell phenotype. The overall purpose of these studies is to deepen our understanding of the processes underlying alveolar stability and to contribute to new concepts and treatments for lung diseases associated with disorders of alveolar stability or epithelial maturation.