ADAPTATION OF RAT TYPE-II PNEUMOCYTES TO NO2 - EFFECTS OF NO2 APPLICATION MODE ON PHOSPHATIDYLCHOLINE METABOLISM

Previous studies have shown that nitrogen dioxide (NO2) inhalation aff ects the extracellular surfactant as well as the structure and functio n of type II pneumocytes. Since in these studies there were great vari abilities in oxidant concentration, duration of exposure, and mode of NO2 application, we evaluated the influence of the NO2 application mod e on the phospholipid metabolism of type II pneumocytes. Rats were exp osed to identical NO2 body doses (720 ppm X h), which were applied con tinuously (10 ppm for 3 d), intermittently (10 ppm for 8 h per day, fo r 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 eva luated for cell yield, vitality, phosphatidylcholine (PC) synthesis, a nd secretion. Type II pneumocyte cell yield from animals that had been continuously exposed to NO2 was significantly increased, whereas inte rmittently and repeatedly treated rats exhibited cell yields that were nonsignificantly enhanced. Vitality of the isolated type II pneumocyt es was not affected by the NO2 exposure modes. Continuous application of 720 ppm X h NO2 resulted in increased activity of the cytidine-5-di phosphate (CDP)-choline pathway. After continuous NO2 application, spe cific activity of choline kinase, cytidine triphosphate (CTP):cholinep hosphate cytidylyltransferase, uptake of choline, and pool sizes of CD P-choline and PC were significantly increased over these of controls. Intermittent application of this NO2 body dose also provoked an increa se in PC synthesis, but this increase was less prominent than after co ntinuous exposure. After repeated exposure, the synthesis parameters w ere comparable to those for cells from control animals. Whereas PC syn thesis in type II cells was obviously stimulated by NO2, the secretory activity of the cells was reduced. Continuous exposure I educed this activity most, whereas intermittent exposure nonsignificantly reduced this activity as compared with that of controls. The repeated applicat ion of NO2 produced no differences. We conclude that type II pneumocyt es 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 ad ditional metabolic activities will also adapt to NO2 atmospheres, and if these observations are specific for NO2 or represent effects genera lly due to oxidants.