Regulation of phosphatidylcholine biosynthesis in activated alveolar type II cells

The biosynthesis of phosphatidylcholine was studied in a population of activated Type II cells isolated from the lungs of rats treated with silica. Type II cells were separated by centrifugal elutriation into two populations, designated Type IIA and Type IIB. The Type IIB or activated population consisted of Type II cells that were larger than normal cells; Type IIA cells were morphologically similar to normal Type II cells. Type IIB cells incorporated more [Me-14C]choline into both total phosphatidylcholine and disaturated phosphatidylcholine than did Type IIA or control Type II cells. Measurement of the pool sizes of the choline-containing precursors to phosphatidylcholine indicated that the biosynthesis of phosphatidylcholine was increased 4- to 5-fold in Type IIB cells. Increased conversion of cholinephosphate to CDP-choline was associated with increased phosphatidylcholine biosynthesis in Type IIB cells. Cholinephosphate cytidylyltransferase activity was increased approximately threefold in Type IIB cells. Subcellular fractionation indicated that essentially all of the increase in cytidylyltransferase activity was associated with the particulate fraction (100,000 x g pellet). In Type IIB cells, the particulate fraction contained 83% of the total cellular cytidylyltransferase activity; in control cells, this fraction contained 67% of the total activity. The specific activity of the cytidylyltransferase associated with the particulate fraction was increased twofold in Type IIB cells. The specific activity of the cytosolic enzyme was similar to that in control cells. Cholinephosphotransferase specific activity was increased approximately twofold in the activated Type II cells. The specific activity of choline kinase was the same as that in control Type II cells. These results demonstrate that the increased biosynthesis of phosphatidylcholine in Type IIB cells is a result of stimulation of the CDP-choline pathway. This study indicates that both cholinephosphate cytidylyltransferase and cholinephosphotransferase may be involved in regulating the de novo biosynthesis of phosphatidylcholine in alveolar Type II cells.