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Nitric Oxide (NO) Synthase Activity in the Lung and NO Synthesis in Alveolar Macrophages of Rats Increased on Exposure to Asbestos
Author(s) -
Iguchi Hiroshi,
Kojo Shosuke,
Ikeda Masayuki
Publication year - 1996
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/(sici)1099-1263(199607)16:4<309::aid-jat345>3.0.co;2-z
Subject(s) - chrysotile , asbestos , nitric oxide synthase , nitric oxide , lipopolysaccharide , chemistry , alveolar macrophage , lung , toxicity , microbiology and biotechnology , andrology , macrophage , biochemistry , immunology , medicine , biology , in vitro , materials science , organic chemistry , metallurgy
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 (Mϕs) 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 Mϕs with CH, NO −2 , 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 Mϕs induced NOS on exposure to CH. Viability of Mϕs was lower in the culture with CH than in the culture with AM or CR. When alveolar Mϕs were cultured in the presence of lipopolysaccharide (LPS), a potent inducer of NOS, NO −2 in the medium dramatically increased, indicating a possible induction of NOS, while NO −2 was decreased significantly in the presence of both LPS and CH, AM or CR. On the other hand, when Mϕs which had previously been stimulated with LPS were cultured in LPS‐free medium, NO −2 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 NO −2 , but not to affect the synthesis of NO −2 by LPS‐induced NOS. Taken altogether, lung or alveolar Mϕs of rats induced NOS to increase NO synthesis on exposure to CH.