Stimulation of prostaglandin synthesis by hyperoxia in perinatal rat lung cells.
Prostaglandins (PGs) have been implicated in the development of pulmonary oxygen toxicity. We tested the hypothesis that hyperoxia modulates PG synthesis in a differentiation-arrested primary lung cell culture model in the rat at three developmental ages: day-20 gestation (term = 22 days), days 1 and 3 after birth. The time courses of the response to hyperoxia were defined in preconfluent lung cells as well as in growth-arrested, confluent cells. From days 4-8 after plating in growth medium containing 10% carbonstripped fetal bovine serum, exposure to 95% O2, in contrast to 1% O2, inhibited cell proliferation but significantly enhanced the production of PGI2 and, to a lesser extent, PGE2 at all three ages. The capacity to metabolize exogenous arachidonic acid (AA) to PGI2 was also increased two-to threefold (P less than 0.01). Cellular release of lactate dehydrogenase, a measure of O2 toxicity, remained unchanged during exposure to 1% O2 but increased fivefold between 48 and 96 h after exposure to hyperoxia (from 2% total to 10.5%, P less than 0.01). In confluent, growtharrested cells, under serum-free conditions, exposure to hyperoxia for 24-48 h resulted in a similar induction of PG synthesis. Our results suggest that hyperoxia stimulates PG synthesis in the perinatal rat lung and that this effect is independent of cell growth or the presence of serum. We speculate that this hyperoxia-induced PG synthesis is a relatively early response to oxidant stress and may serve as an useful early marker for O2 toxicity in perinatal lung cells.
Lee
D S
DS
Department of Paediatrics, Lawson Research Institute, University of Western Ontario, London, Canada.
Bevan
M G
MG
Olson
D M
DM
D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D011464:Epoprostenol / Q000096:biosynthesis*; D005333:Fetus; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D011464:Epoprostenol; D015232:Dinoprostone; D010100:Oxygen