MAINTENANCE OF THE DIFFERENTIATED TYPE-II CELL PHENOTYPE BY CULTURE WITH AN APICAL AIR-SURFACE

The study of differentiated functions of alveolar type II cells has be en hampered because of the lack of good in vitro systems. We report th at culture of type II cells on collagen gels with an apical surface ex posed to air promotes expression of differentiated type II cell charac teristics. Cells cultured in this manner are cuboidal, contain lamella r bodies, and produce tubular myelin; in addition, they secrete phosph atidylcholine in response to exogenous ATP. Cultures contain mRNA for surfactant proteins A, B, and C and surfactant proteins A, B, and D. I n contrast, when type II cells are cultured with an apical surface exp osed to liquid rather than to air, the cells are squamous, do not expr ess surfactant proteins or their respective mRNA, and do not contain l amellar bodies or produce tubular myelin. Type II cells cultured on pl astic for 7 days, which no longer express mRNA for surfactant proteins , can be induced to express these mRNA by changing culture conditions to that of an air surface. The culture system described in this paper should be useful for studies of surfactant metabolism, regulation of a lveolar epithelial phenotypic expression, and the processing of transi ently expressed transgenes.