Nitric oxide mediates the microbicidal activity of eosinophils.
There are several experimental evidences that nitric oxide (NO) is involved in the microbicidal activity of macrophages against a number of intracellular pathogens including Leishmania major, Trypanozoma cruzi, Toxoplasma gondii. It is also well known that eosinophils (EO) have microbicidal activity against many parasites such as Schistosoma mansoni, Trichinella spiralis, T. cruzi and L. amazonensis. The purpose of this study was to investigate if NO is involved in the microbicidal activity of EO against L. major. Eosinophils harvested from peritoneal cavity of rats released spontaneously after 24 and 48 hr a small amount of nitrite. This release was enhanced by the treatment of cells with IFN-gamma (200 IU/ml). This release was blocked by addition of the NO synthase inhibitor, L-NIO (100 microM) into the culture. To determinate the leishmanicidal activity of eosinophils the parasites were incubated with activated eosinophils with IFN-gamma and the ability of surviving parasites to incorporate [(3)H] thymidine was evaluated. IFN-gamma-activated eosinophils were able to kill L. major and to release high levels of nitrite. The ability to destroy L. major and the release of NO were completely blocked by L-NIO. These results indicate that activated eosinophils release NO which is involved in the microbicidal activity of these cells against L. major.
Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil.
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Oliveira
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Fonseca
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Romão
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Ferreira
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Cunha
D000704:Analysis of Variance; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D004804:Eosinophils / Q000502:physiology*; D007371:Interferon-gamma; D018320:Leishmania major; D009569:Nitric Oxide / Q000502:physiology*; D009952:Ornithine / Q000031:analogs & derivatives / Q000187:drug effects; D010529:Peritoneal Cavity; D051381:Rats
D000998:Antiviral Agents; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D007371:Interferon-gamma; D009952:Ornithine