IMPAIRED SURFACTANT SYNTHESIS IN FETAL TYPE-II LUNG-CELLS FROM GSD GSD RATS/

The importance of intracellular glycogen for surfactant synthesis was investigated in fetal type II lung cells isolated from rats with a gly cogen storage disorder, designated gsd/gsd. Compared to cells from a c ontrol Wistar strain, cultured gsd/gsd pneumocytes were glycogen-rich and contained fewer and smaller lamellar inclusions. Freshly isolated cells from day 19-21 fetuses of control rats demonstrated the expected gestational rise and fall of cellular glycogen seen in intact fetal l ungs. At day 20, when tissue glycogen peaks, cellular glycogen content was 48 and 70 nmol glucose/mu g DNA in isolated type II cells of cont rol and gsd/gsd lungs, respectively. In control cells, while active gl ycogen phosphorylase changed from 35 to 65% of total during 24 h of cu lture, glycogen fell 85%. In contrast, gsd/gsd cell phosphorylase was not activated, phosphorylase kinase activity was nondetectable, and gl ycogen per cell remained unchanged. [H-3]Choline incorporation into to tal PC and disaturated PC (DSPC) was 50 and 62% lower, respectively, i n gsd/gsd type II cells compared to controls in the absence of exogeno us substrate. Cellular content of the surfactant-associated protein SP -A was similar in control and gsd/gsd cells at day 20, and increased 3 - to 4-fold during a subsequent 24-h interval of tissue culture. These results suggest that PC synthesis is dramatically impaired in type II cells in which glycogen cannot be mobilized, but SP-A is synthesized at normal rates. This work characterizes the isolated gsd/gsd fetal ty pe II cell and supports its use in future studies to determine the imp ortance and relative utilization of specific nonglycogen substrates.