Epithelial-interstitial cell interactions in fetal rat lung development accelerated by steroids.

Direct cell to cell contact has been suggested as the means whereby fibroblast factors influence epithelial cell differentiation in the developing lung. To obtain further evidence for this hypothesis, the role of epithelial-mesenchymal cell contacts is now examined when lung development is accelerated after steroid injection. Male and female rat fetuses were studied from day 17 to day 22 of gestation. The fetuses were from mothers injected with 2 mg/kg of dexamethasone at 2 days before death and [3H]thymidine at 1 hour before death. Steroid injected during the rapid growth phase reduced total DNA in fetal lung, and from autoradiographs, the effect was most noticeable in epithelial cells. Differentiation began sooner after steroid; more epithelial cells contained lamellar bodies and disaturated phosphatidylcholine levels were higher. From quantitative ultrastructural studies, these changes in phospholipid correlated with an increased frequency of epithelial-interstitial cell contacts. Steroid treatment did not abolish the sex-related difference seen in controls; both males and females showed increases in cell to cell contacts and in lipid synthesis in the lung. The results demonstrate that acceleration of epithelial cell maturation with increased surfactant synthesis is associated with increased epithelial-interstitial cell contacts. This supports the concept that regulatory messages from the fetal fibroblast are passed directly to specific epithelial cells to initiate surfactant synthesis.