FATTY-ACID SYNTHASE ACTIVITY AND MESSENGER-RNA LEVEL IN HYPERTROPHIC TYPE-II CELLS FROM SILICA-TREATED RATS

Silica instillation causes a massive increase in lung surfactant. Two populations of type II pneumocytes can be isolated from rats administe red silica by intratracheal injection: type IIA cells similar to type II cells from normal rats and type IIB cells, which are larger and con tain elevated levels of surfactant protein A and phospholipid. Activit ies of choline-phosphate cytidylyltransferase, a rate-regulatory enzym e in phosphatidylcholine biosynthesis, and fatty-acid synthase (FAS) a re increased in type IIB cells isolated from rats 14 days after silica injection. In the present study, we examined the increases in FAS and cytidylyltransferase activities in type IIB cells as a function of ti me after silica administration. FAS activity increased rapidly, was ap proximately threefold elevated 1 day after silica administration and h as reached close to the maximum increase by 3 days. Cytidylyltransfera se activity was not increased on day 1, was significantly increased on day 3 but was not maximally increased until day 7. Inhibition of de n ovo fatty-acid biosynthesis, by in vivo injection of hydroxycitric aci d and inclusion of agaric acid in the type II cell culture medium, abo lished the increase in cytidylyltransferase activity on day 3 but not FAS and had no effect on activities of two other enzymes of phospholip id synthesis. FAS mRNA levels were not increased in type IIB cells iso lated 1-14 days after silica injection. These data show that the incre ase in FAS activity in type IIB cells is an early response to silica, that it mediates the increase in cytidylyltransferase activity, and th at it is not due to enhanced FAS gene expression.