Long-term effects of ozone and nitrogen dioxide on the metabolism and population of alveolar macrophages.
To investigate how alveolar macrophages adapt themselves to oxidative pollutants in the long term, rats were exposed to a strong oxidant, ozone (O3), or a weak oxidant, nitrogen dioxide (NO2), for a maximum duration of 12 wk. After exposures, alveolar macrophages were collected by pulmonary lavage. Throughout 11 wk of exposure to 0.2 ppm O3, the specific activities of glucose-6-phosphate dehydrogenase (G6PDH) and glutathione peroxidase of the peroxidative metabolic pathway and pyruvate kinase and hexokinase of the glycolytic pathway were 40-70% elevated over the controls in alveolar macrophages. The population of alveolar macrophages was consistently 60% higher than the controls. The small-sized macrophages, immature macrophages, preferentially increased. To the contrary, the thymidine incorporation per cell was always 20-30% lower than in the controls, although the total incorporation remained unchanged. No infiltration of polymorphonuclear leukocytes occurred. By 12 wk of exposures to 1.2 and 4.0 ppm NO2, the population of alveolar macrophages increased 30% over the control. Among the enzymes examined, however, only the G6PDH activity increased 10% for 4.0 ppm NO2. No increase in the enzyme activities occurred for 1.2 ppm NO2. Based on these results, alveolar macrophages adapt themselves to the long-term exposure of O3 or NO2 by recruiting immature macrophages through an apparent influx of monocytes. During the exposure to O3, the peroxidative metabolic and glycolytic pathways are enhanced persistently in alveolar macrophages, whereas both pathways were not enhanced by the exposures to NO2.
Mochitate
K
K
Environmental Health Sciences Division, National Institute for Environmental Studies, Ibaraki, Japan.
Ishida
K
K
Ohsumi
T
T
Miura
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005954:Glucosephosphate Dehydrogenase / Q000032:analysis; D005979:Glutathione Peroxidase / Q000032:analysis; D006019:Glycolysis; D006593:Hexokinase / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009585:Nitrogen Dioxide / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D014176:Protein Biosynthesis; D011770:Pyruvate Kinase / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013047:Specific Pathogen-Free Organisms
D010126:Ozone; D000255:Adenosine Triphosphate; D004247:DNA; D007770:L-Lactate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D006593:Hexokinase; D011770:Pyruvate Kinase; D009585:Nitrogen Dioxide