ONTOGENY OF SURFACTANT PROTEINS AND LIPID-SYNTHESIZING ENZYMES IN CULTURED FETAL LUNG EPITHELIAL-CELLS

Fetal rat lung epithelial cells were isolated on gestational day 17 (t erm is 22), separated from fibroblasts, and cultured up to 6 days in a serum-free medium on a basement membrane matrix. Surfactant protein ( SP) A, barely detectable by immunostaining at the beginning of the cul ture, considerably increased in cells and subsequently in the lumen of the epithelial cell clusters. SP-A mRNA, already detectable at cultur e initiation, progressively increased. By contrast, SP-B and its mRNA appeared after 2-3 days. SP-C mRNA appeared only after 4 days of cultu re. Cells cultured 6 days had a phospholipid composition similar to th at of freshly isolated adult rat type II cells. The enhancement of lip id synthesis between the first and the sixth culture days, reported ea rlier to occur in these cells, was found to be accompanied by a two- t o fivefold increase in amount of mRNAs of lipogenic enzymes and cholin e phosphate cytidylyltransferase. In conclusion, alveolar epithelial t ype II cells appear to be capable of full differentiation in vitro, an d components of the surfactant system are all regulated developmentall y at a pretranslational level.