DEVELOPMENTAL REGULATION OF THE EFFECTS OF SURFACTANT PROTEIN-A ON PHOSPHOLIPID UPTAKE BY FETAL-RAT TYPE-II PNEUMOCYTES

Surfactant protein A (SP-A) enhances the uptake of phospholipid by typ e II cells derived from adult and late gestation fetal rat lung. The p resent study was performed to examine more fully the developmental bio logy of the effects of SP-A on phosphatidylcholine (PC) uptake, to det ermine the effect of SP-A on the cellular location of bound and intern alized phospholipid and on the metabolism of internalized phospholipid by morphologically undifferentiated (18-day) and morphologically diff erentiated (19-day) fetal type II cells. SP-A enhanced uptake almost t wofold in a dose-dependent manner in 19-day fetal cells, but it had no effect on uptake by Is-day fetal cells at any concentration. Stimulat ion of uptake by 19-day fetal cells was saturable at concentrations ab ove 1 mu g/ml SP-A. Maximal uptake was 1.12 nmol of PC/mg of protein, and the effective concentration that yields 50% maximal response, K-Ph i, was 58.9 ng/ml (84.1 pM). The effect of SP-A on uptake by 19-day fe tal cells was detectable as early as 1 min of exposure. Uptake correla ted significantly with time both in the absence (r = 0.98, p < 0.001) and presence of 5 mu g/ml SP-A (r = 0.979, p < 0.001). The rate of upt ake in the presence of SP-A (0.019 +/- 0.002 nmol of PC/mg of protein/ min) was twice the rate of uptake in controls (0.009 +/- 0.001 nmol of PC/mg of protein/min). SP-A had no effect on binding to plasma membra nes and uptake of phospholipid into lamellar bodies by 18-day fetal ce lls. On the other hand, SP-A significantly enhanced binding of dipalmi toyl phosphatidylcholine to plasma membranes (two-to threefold) and up take into lamellar bodies (threefold) of 19-day fetal cells. SP-A caus ed a significant reduction in the degradation of internalized phosphol ipid by differentiated fetal type LI cells. Based on the lack of effec t of exogenous SP-A on Is-day fetal cells, we conclude that the respon se to SP-A is under developmental control. SP-A enhances the initial b inding to the plasma membranes of fetal type II cells and subsequent i nternalization into the lamellar bodies. This effect is associated wit h a protection of internalized phospholipid from metabolic degradation . Both of these processes are developmentally regulated during the tra nsition from the canalicular to the saccular phase of lung development .