Uptake of ³H Prednisolone by Fetal Lung Explants: Role of Intercellular Contacts in Epithelial Maturation

Abstract

Epithelial maturation in the developing lung is accelerated by glucocorticoids and it has been suggested that a fibroblast-derived factor may be important in regulating this response. In the present study, uptake of ³H prednisolone by cultured explants of fetal rat lung is used to correlate cellular location of the steroid with changes in epithelial–-mesenchymal cell relationships at different stages of development. At days 17 and 18 of gestation, there is substantial incorporation of steroid by epithelial and interstitial cells with no morphologic evidence of accelerated maturation. At days 19 and 20, uptake of prednisolone is maximal with preferential incorporation by Type 2 cells which now contain an increased number of lamellar bodies. In the bronchioles, steroid uptake is observed in Clara cells but not in ciliated cells. Lung development results in a progressively closer anatomic relationship between alveolar epithelial and interstitial cells andat the time of maximal steroid response, day 19–20, narrow “gap junctions” are observed between these cell types. The results suggest that, although steroid is bound to several cell types from an early stage of development, the effects on epithelial maturation occur relatively late in gestation when close epithelial-mesenchymal cell contacts are made.