FETAL-RAT LUNG TYPE-II CELL-DIFFERENTIATION IN SERUM-FREE ISOLATED CELL-CULTURE - MODULATION AND INHIBITION

Undifferentiated fetal rat lung epithelial cells were isolated on gest ational days 15 or 17 (term 22 days) and cultured in a defined medium. On plastic, most of the cells developed structurally abnormal lamella r bodies. On a basement membrane matrix (BMM), they sequentially accum ulated glycogen and formed typical lamellar bodies. Biochemical analys is of the latter indicated that they had a phospholipid composition ty pical of surfactant for cells on BMM but not on plastic and that surfa ctant protein A appeared on BMM only. Progressing maturation from day 1 to day 6 in culture was demonstrated for 17-day cells on BMM by a se venfold increase of labeled precursor incorporation into surfactant ph ospholipids. Exposure to medium conditioned by 21-day fetal fibroblast s enhanced incorporation already after a 1-day culture. The antisteroi d RU 486 had no effect on differentiation, whereas transforming growth factor-beta, a factor produced by lung mesenchyme at early fetal stag es, inhibited it markedly. Alveolar epithelial type II cells appear to be committed early, but their maturational process would be prevented until a definite gestational stage.