Stimulation of surfactant phospholipid biosynthesis in the lungs of rats treated with silica.
The effects of intratracheally instilled silica (10 mg/rat) on the biosynthesis of surfactant phospholipids was investigated in the lungs of rats. The sizes of the intracellular and extracellular pools of surfactant phospholipids were measured 7, 14 and 28 days after silica exposure. The ability of lung slices to incorporate [14C]choline and [3H]palmitate into surfactant phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) was also investigated. Both intra- and extra-cellular pools of surfactant phospholipids were increased by silica treatment. The intracellular pool increased linearly over the 28-day time period, ultimately reaching a size 62-fold greater than controls. The extracellular pool also increased, but showed a pattern different from that of the intracellular pool. The extracellular pool increased non-linearly up to 14 days, and then declined. At its maximum, the extracellular pool was increased 16-fold over the control. The ability of lung slices to incorporate phospholipid precursors into surfactant-associated PC and DSPC was elevated at all time periods. The rate of incorporation of [14C]choline into surfactant PC and DSPC was maximal at 14 days and was nearly 3-fold greater than the rate in controls. The rate of incorporation of [3H]palmitate was also maximal at 14 days, approx. 5-fold above controls for PC and 3-fold for DSPC. At this same time point, the microsomal activity of cholinephosphate cytidylyltransferase was increased 4.5-fold above controls, but cytosolic activity was not significantly affected by silica treatment. These data indicate that biosynthesis of surfactant PC is elevated after treatment of lungs with silica and that this increased biosynthesis probably underlies the expansion of the intra- and extra-cellular pools of surfactant phospholipids.
Miller
B E
BE
Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Hook
G E
GE
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002794:Choline / Q000378:metabolism; D019916:Choline-Phosphate Cytidylyltransferase; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009713:Nucleotidyltransferases / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D012822:Silicon Dioxide / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D010169:Palmitic Acids; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; C017463:lecithins, disaturated; D019308:Palmitic Acid; D012822:Silicon Dioxide; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; D002794:Choline