Nitric oxide (NO) synthase activity in the lung and NO synthesis in alveolar macrophages of rats increased on exposure to asbestos.
We examined whether the lung of rats induced nitric oxide synthase (NOS) on instillation of Union Internationale Contre le Cancer (UICC) asbestos into the trachea, and whether alveolar macrophages (M phi s) of rats increased synthesis of nitric oxide (NO) on exposure to the asbestos. Instillation of chrysotile asbestos (CH) into rat tracheas increased NOS activity in the lung up to fourfold compared with that of normal control rats. On instillation of amosite asbestos (AM), the activity did not significantly increase. In the culture of alveolar M phi s with CH, NO2-, a stable oxidation product of NO, in the conditioned medium markedly increased while in the culture with AM or crocidolite (CR) asbestos it was comparable to that in the control culture without asbestos. Thus, it was assumed that the lung as well as alveolar M phi s induced NOS on exposure to CH. Viability of M phi s was lower in the culture with CH than in the culture with AM or CR. When alveolar M phi s were cultured in the presence of lipopolysaccharide (LPS), a potent inducer of NOS, NO2- in the medium dramatically increased, indicating a possible induction of NOS, while NO2- was decreased significantly in the presence of both LPS and CH, AM or CR. On the other hand, when M phi s which had previously been stimulated with LPS were cultured in LPS-free medium, NO2- synthesis retained a significantly increased level, irrespective of the presence or absence of asbestos. Thus, the three kinds of asbestos used seemed to interfere with LPS in inducing NOS and to decrease subsequently the synthesis of NO2-, but not to affect the synthesis of NO2- by LPS-induced NOS. Taken altogether, lung or alveolar M phi s of rats induced NOS to increase NO synthesis on exposure to CH.
Iguchi
H
H
Department of Public Health, Faculty of Medicine, Kyoto University, Japan.
Kojo
S
S
Ikeda
M
M
D000818:Animals; D001194:Asbestos / Q000009:adverse effects*; D017639:Asbestos, Amosite / Q000633:toxicity; D017638:Asbestos, Crocidolite / Q000009:adverse effects; D017632:Asbestos, Serpentine / Q000009:adverse effects; D002273:Carcinogens / Q000009:adverse effects*; D004347:Drug Interactions; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000201:enzymology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D017632:Asbestos, Serpentine; D002273:Carcinogens; D008070:Lipopolysaccharides; D017638:Asbestos, Crocidolite; D017639:Asbestos, Amosite; D001194:Asbestos; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase