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KMID : 0385219950050020072
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Korean Journal of Gerontology
1995 Volume.5 No. 2 p.72 ~ p.79
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Inhibition of Nitric Oxide Generation from Macrophanges by Cadmium
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Kwon Tae-Woo
Lee Eun-A
Chi Kyong-Chon
Baek Kwang-Jin
Kwon Nyoun-Soo
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Abstract
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Cadmium, a toxic heavy metal, has been known to cause many harmful effects on human health including impairment of cell-mediated immunity. In the present study, an effect of cadmium on nitric oxide (NO) generation from macrophages was studied NO has been proved to play an important role in antitumor and antimicrobial activities of macrophages, when macrophages-like RAW 264.7 cells were treated with different concentrations of cadmium ranging from 1 to 10 ㎛ and followed by stimulation with lipopolysaccharide and interferon-Υ the NO generation by macrophages was inhibited by a dose-dependent manner. The inhibitory effect of NO generation by macrophages pre-treated with cadmium far exceeded the cytotoxic effect, suggesting that the cadmium acts on macrophages to reduce the NO synthesis. The difference between degrees of inhibition of NO generation and the viability of macrophages by cadmium was much more prominent in murine peritoneal macrophages. Immunoblotting analyses showed that cadmium did not affect on the expression of NO synthase protein. Lysate from cadmium-treated macrophages exhibited decreased NOS activity and decreased level of heme, which is a component of NO synthase. These results suggested that cadmium might not prevent the expression of NO synthsse, but might prevent formation of fully active enzyme probably by means of decreasing heme concentration. Furthermore, NO generating activity of macrophages lysate was markedly inhibited by 10 or 50 μM cadmium, suggesting that the direct inhibitory effect of cadmium on NO synthase might result in the decrease of NO generation.
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KEYWORD
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cadmium, macrophages, nitric oxide
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