HUMAN-FETAL LUNG TYPE-II PNEUMONOCYTES IN MONOLAYER CELL-CULTURE - INFLUENCE OF OXIDANT STRESS, CORTISOL ENVIRONMENT, AND SOLUBLE FIBROBLAST FACTORS

A pure culture of human fetal lung type II pneumonocytes has been developed and labeled HFLP. Cells were studied during the period of exponential growth that was observed to occur in this system from day 4 to day 8 after subculture. Correlations with exponential growth were highly significant (P < 0.001) in all groups studied. Growth was not greatly different at any of the different oxygen tensions (30, 55, 80, and 145 mm Hg) examined except that growth was slightly more rapid at a PO2 of 145 mm Hg than at a PO2 of 80 mm Hg (P < 0.05). The uptake of3H- choline into DSPC at a PO2 of 30 mm Hg was significantly less than at 55 mm Hg (P < 0.001) or 80 mm Hg (P < 0.001), whereas the uptake at 145 mm Hg was also significantly less than that at 55 mm Hg (P < 0.001) or 80 mm Hg (P < 0.001). Uptake at 55 and 90 mm Hg was not significantly different. The response to added cortisol (1 μM) also varied with the oxygen tension, with no effect at a PO2 of 30 mm Hg while, at a PO2 of 55 mm Hg the SH- choline uptake was significantly different on day 5 (P < 0.001), day 6 (P < 0.001) and day 7 (P < 0.01). Similarly, at a PO2 of 80 mm Hg the difference was significant on day 5 (P < 0.05), day 6 (P < 0.01) and day 7 (P < 0.01). At a PO2 of 145 mm Hg, the difference was just significant on day 7 (P < 0.05). In isolated HFLP cells, an oxidant challenge produced by increasing PO2 from 30 to 55 mm Hg resulted in a 96% increase in3H-choline uptake in both the control group (P< 0.001) and the steroid-added group (P< 0.001). In the combined HFLP and fetal lung fibroblast culture there was a 275% increase over the uptake before oxidant challenge after 48 hr (control group P < 0.001, steroid group P < 0.001). In the experiment where HFLP cells were grown in the presence of 10% fibroblast-derived medium, the increase after 48 hr was 135% over values before the oxidant challenge (control group P < 0.001). In this experiment, the steroid-added group had an increased response compared to the control group 48 hr after the oxidant challenge (P < 0.02). Speculation: It was speculated that the type II pneumonocyte requires an unknown cofactor in order to respond to antenatal steroid treatment by increased production of surface active materials. It was further speculated that the change of PO2 that occurs in pulmonary tissue after delivery acts as an important biologic stimulus to cause increased production of surface active materials, and that this mechanism can be favorably enhanced by pretreatment with steroids, and is mediated in part by soluble factor(s) derived from the fetal lung fibroblast. © 1979 International Pediatric Research Foundation, Inc.