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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL024075-14
Application #
3097861
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1979-07-01
Project End
1994-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
14
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Barrette, Anne Marie; Roberts, Jessica K; Chapin, Cheryl et al. (2016) Antiinflammatory Effects of Budesonide in Human Fetal Lung. Am J Respir Cell Mol Biol 55:623-632
Danhaive, Olivier; Chapin, Cheryl; Horneman, Hart et al. (2015) Surface film formation in vitro by infant and therapeutic surfactants: role of surfactant protein B. Pediatr Res 77:340-6
Vanderbilt, Jeff N; Gonzalez, Robert F; Allen, Lennell et al. (2015) High-efficiency type II cell-enhanced green fluorescent protein expression facilitates cellular identification, tracking, and isolation. Am J Respir Cell Mol Biol 53:14-21
Gonzales, Linda W; Gonzalez, Robert; Barrette, Anne Marie et al. (2015) Expression of Carcinoembryonic Cell Adhesion Molecule 6 and Alveolar Epithelial Cell Markers in Lungs of Human Infants with Chronic Lung Disease. J Histochem Cytochem 63:908-21
Raymond, Wilfred W; Xu, Xiang; Nimishakavi, Shilpa et al. (2015) Regulation of hepatocyte growth factor in mice with pneumonia by peptidases and trans-alveolar flux. PLoS One 10:e0125797
LaFemina, Michael J; Sutherland, Katherine M; Bentley, Trevor et al. (2014) Claudin-18 deficiency results in alveolar barrier dysfunction and impaired alveologenesis in mice. Am J Respir Cell Mol Biol 51:550-8
Gonzalez, Robert F; Dobbs, Leland G (2013) Isolation and culture of alveolar epithelial Type I and Type II cells from rat lungs. Methods Mol Biol 945:145-59
Chapin, Cheryl; Bailey, Nicole A; Gonzales, Linda W et al. (2012) Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung. Am J Physiol Lung Cell Mol Physiol 302:L216-25
Heine, Vivi M; Griveau, Amelie; Chapin, Cheryl et al. (2011) A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury. Sci Transl Med 3:105ra104
Gonzalez, Robert F; Allen, Lennell; Gonzales, Linda et al. (2010) HTII-280, a biomarker specific to the apical plasma membrane of human lung alveolar type II cells. J Histochem Cytochem 58:891-901

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