title: Adaptation of rat type II pneumocytes to NO2: effects of NO2 application mode on phosphatidylcholine metabolism.
abstract: Previous studies have shown that nitrogen dioxide (NO2) inhalation affects the extracellular surfactant as well as the structure and function of type II pneumocytes. Since in these studies there were great variabilities in oxidant concentration, duration of exposure, and mode of NO2 application, we evaluated the influence of the NO2 application mode on the phospholipid metabolism of type II pneumocytes. Rats were exposed to identical NO2 body doses (720 ppm x h), which were applied continuously (10 ppm for 3 d), intermittently (10 ppm for 8 h per day, for 9 d), and repeatedly (10 ppm for 3 d, 28 d rest, and then 10 ppm for 3 d). Immediately after exposure, type II cells were isolated and evaluated for cell yield, vitality, phosphatidylcholine (PC) synthesis, and secretion. Type II pneumocyte cell yield from animals that had been continuously exposed to NO2 was significantly increased, whereas intermittently and repeatedly treated rats exhibited cell yields that were nonsignificantly enhanced. Vitality of the isolated type II pneumocytes was not affected by the NO2 exposure modes. Continuous application of 720 ppm x h NO2 resulted in increased activity of the cytidine-5-diphosphate (CDP)-choline pathway. After continuous NO2 application, specific activity of choline kinase, cytidine triphosphate (CTP):cholinephosphate cytidylyltransferase, uptake of choline, and pool sizes of CDP-choline and PC were significantly increased over those of controls. Intermittent application of this NO2 body dose also provoked an increase in PC synthesis, but this increase was less prominent than after continuous exposure. After repeated exposure, the synthesis parameters were comparable to those for cells from control animals. Whereas PC synthesis in type II cells was obviously stimulated by NO2, the secretory activity of the cells was reduced. Continuous exposure reduced this activity most, whereas intermittent exposure nonsignificantly reduced this activity as compared with that of controls. The repeated application of NO2 produced no differences. We conclude that type II pneumocytes adapt to NO2 atmospheres depending on the mode of its application, at least for the metabolism of PC and its secretion from isolated type II pneumocytes. Further studies are necessary to determine whether additional metabolic activities will also adapt to NO2 atmospheres, and if these observations are specific for NO2 or represent effects generally due to oxidants.
authors.affiliation: Laboratory of Respiratory Cell Biology, Department of Internal Medicine, and Institute of Pathology, Philipps University of Marburg, Marburg, Germany. bmueller@mailer.uni-marburg.de
authors.forename: B
authors.initials: B
authors.lastname: Müller
authors.forename: C
authors.initials: C
authors.lastname: Seifart
authors.forename: P
authors.initials: P
authors.lastname: von Wichert
authors.forename: P J
authors.initials: PJ
authors.lastname: Barth
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D002797:Choline Kinase / Q000378:metabolism; D019916:Choline-Phosphate Cytidylyltransferase / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D009585:Nitrogen Dioxide / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000378:metabolism
chemical_list: D010713:Phosphatidylcholines; D010743:Phospholipids; D013501:Surface-Active Agents; D007770:L-Lactate Dehydrogenase; D002797:Choline Kinase; D019916:Choline-Phosphate Cytidylyltransferase; D009585:Nitrogen Dioxide