Am. J. Respir. Cell Mol. Biol.,
Volume 18, Number 5, May, 1998 712-720
Adaptation of Rat Type II Pneumocytes to NO2: Effects of NO2 Application
Mode on Phosphatidylcholine Metabolism
Bernd
Müller,
Carola
Seifart,
Peter
von Wichert,
and
Peter J.
Barth
Laboratory of Respiratory Cell Biology, Department of Internal Medicine, and Institute of Pathology,
Philipps University of Marburg, Marburg, Germany
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 × 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 × 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.
