Reciprocal Epithelial: Fibroblast Interactions in the Control of Fetal and Adult Rat Lung Cells in Culture

Intercellular communication between epithelial cells and fibroblasts of the alveolar wall has been postulated from studies of lung development and repair. We examined the epithelial cell-fibroblast interactions with respect to growth control and epithelial cell function using cultured fetal and adult lung cells. The role of diffusing factor(s) as compared to direct cell-to-cell contact was studied by culturing epithelial cells either on a permeable culture well insert over fibroblasts or in co-culture with fibroblasts. The results show that the normal low proliferative rate of epithelial cells in culture is increased when exposed to fibroblast supernatants. In contrast, epithelial cells (particularly from adult lung) secrete a factor that suppresses fibroblast growth when cultured with a filter between the cell types. However, when cell-cell contact occurs in co-culture, the growth rate of fibroblasts is greatly increased. Synthesis of disaturated phosphatidylcholine by epithelial cells is increased under serum-free conditions and further rises when fetal epithelial cells are exposed to steroid-treated fibroblasts, when the cell types are separated, and when cells are in contact. This indicates that a fibroblast-derived factor stimulates epithelial differentiation, and morphologic evidence relating the appearance of lamellar bodies to the areas of direct epithelial cell-fibroblast contact was found. The results indicate the complex interdependence of these two types of cell where a secretory product of one cell or direct cell-cell contact may alter when regulatory control of the other cell type. These interactions are likely to be important in orderly development and in the reparative response of the lung to injury.