Enhanced fatty acid biosynthesis and normal surfactant secretion in hypertrophic rat type II cells.
Silica instillation causes lung surfactant accumulation as well as hyperplasia and hypertrophy of type II pneumocytes. Two populations of type II cells can be isolated from silica-treated rats: type IIA, which are similar to type II cells from normal animals and type IIB, which are larger and have a higher rate of phosphatidylcholine biosynthesis. We have compared fatty acid biosynthesis and phosphatidylcholine secretion in types IIA and IIB cells and in type II cells from control rats. The cells were isolated by elastase digestion and panning on immunoglobulin G-coated plates and fractionated into types IIA and IIB by centrifugal elutriation. Type IIB cells contained more phospholipid and had an enhanced rate of [3H]choline incorporation into phosphatidylcholine. The activity of choline-phosphate cytidylyltransferase was elevated in the type IIB cells and the extent of the increase was diminished when phosphatidylglycerol was included in the assay, suggesting that the enhanced activity was due to enzyme activation rather than protein synthesis. The basal rate of phosphatidylcholine secretion was the same in all three groups as was the response to a variety of secretagogues. Incorporation of [3H]acetate into fatty acids was elevated in type IIB cells and the activity of fatty acid synthase was eightfold greater than in control cells. These data show that de novo fatty acid biosynthesis is increased in hypertrophic type II cells and that surfactant secretion is not elevated.
Rami
J
J
Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut 06510.
Sasic
S M
SM
Rooney
S A
SA
D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism; D000085:Acetates / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D019916:Choline-Phosphate Cytidylyltransferase; D004247:DNA / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D005227:Fatty Acids / Q000096:biosynthesis*; D006984:Hypertrophy; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009713:Nucleotidyltransferases / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000302:isolation & purification / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012822:Silicon Dioxide / Q000633:toxicity*; D013726:Terbutaline / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000085:Acetates; D004075:Diglycerides; D005227:Fatty Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D011506:Proteins; D011663:Pulmonary Surfactants; D019830:Adenosine-5'-(N-ethylcarboxamide); D015759:Ionomycin; D012822:Silicon Dioxide; D000255:Adenosine Triphosphate; D004247:DNA; D001275:ATP Citrate (pro-S)-Lyase; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; D000241:Adenosine; D013726:Terbutaline; D002794:Choline; D013755:Tetradecanoylphorbol Acetate