The hypothesis, on which this proposal is based, is that the isolation and study of isolated human type II cells will provide and important new approach to the study of human lung diseases which involve the alveolar epithelium. The alveolar type II cell is an important lung cell with a number of metabolic functions which include the synthesis and secretion of pulmonary surface active material, proliferation after lung injury, and active transepithelial transport of fluid and electrolytes. Studies with type II cells isolated from animals have been unvaluable but are relevant only to the extent that they represent human type II cell function. In this proposal the methods for isolating and culturing human type II cells, developed over the past 12 months in our laboratory will be refined with specific emphasis on the removal of contaminating macrophages and on the maintenance of differentiated function of the cells in culture. In addition, culture conditions which stimulate proliferation of type II cells will be sought. The regulation of type II cell proliferation, important for alveolar epithelial repair, will be studied by the effect of conditioned medium from other cultured lung cells (macrophages and fibroblasts) and from short term organ cultures, on human type II cell proliferation. Bronchoalveolar lavage fluid obtained from patients with both ARDS and ILD will be tested for proliferative activity. We will characterize the proteins secreted by type II cells which are important components of several of the known functions to type II cells and may also be markers for type II cells in bronchoalveolar lavage fluid. We will continue our studies to develop monoclonal antibodies specific for human type II cells. These antibodies would have numerous applications in the isolation and identification of type II cells. In this proposal, we have addressed some of the major goals of the RFA. We consider that the isolation and characterization of human alveolar type II cells will provide an important in vitro system, which will complement other research into the mechanisms of human lung disease at the alveolar level.
| Mason, R J; Apostolou, S; Power, J et al. (1990) Human alveolar type II cells: stimulation of DNA synthesis by insulin and endothelial cell growth supplement. Am J Respir Cell Mol Biol 3:571-7 |
| Miller, Y E; Walker, S R; Spencer, J S et al. (1989) Monoclonal antibodies specific for antigens expressed by rat type II alveolar epithelial and nonciliated bronchiolar cells. Exp Lung Res 15:635-49 |
| Edelson, J D; Shannon, J M; Mason, R J (1989) Effects of two extracellular matrices on morphologic and biochemical properties of human type II cells in vitro. Am Rev Respir Dis 140:1398-404 |
| Mason, R J (1987) Surfactant in adult respiratory distress syndrome. Eur J Respir Dis Suppl 153:229-36 |
| Mason, R J (1987) Surfactant synthesis, secretion, and function in alveoli and small airways. Review of the physiologic basis for pharmacologic intervention. Respiration 51 Suppl 1:3-9 |
| Mason, R J (1985) Pulmonary alveolar type II epithelial cells and adult respiratory distress syndrome. West J Med 143:611-5 |
