Pulmonary alveolar type II epithelial cells exhibit several specialized functions, one of which is the synthesis and secretion of surface active material. Studies of how the production of surface active material is regulated in the intact lung are hampered by the fact that type II cells constitute only 15% of the total lung cell population. Techniques for the isolation and purification of type II cells from adult rat lungs have been developed, yet attempts at maintaining differentiated function of type II cells in vitro have met with little success. This """"""""dedifferentiation"""""""" of type II cells in culture is not unlike that seen in other cultured epithelial cells. However, successful maintenance of differentiation in other cultured epithelia has been achieved under conditions that better simulate the in vivo environment of these cells. I will employ a similar strategy for the maintenance of differentiation of type II cells in vitro. I will examine phospholipid synthesis and secretion, as well as ultrastructure, in type II cells cultured under heretofore untested conditions. I will evaluate four general factors that may affect type II cell differentiation: interaction of type II cells with specialized substrate (extracellular matrices), interaction of type II cells with lung and non-lung mesenchymal cells, maintenance of cuboidal cell shape, and effects of hormones and other soluble factors. My preliminary data imply that all of these factors may be involved in the maintenance of type II cell differentiated function. The proposed studies not only address basic problems in epithelial cell biology, but are also crucial to developing a system for studying all facets of type II cell function.
