Role of peroxynitrite in macrophage microbicidal mechanisms in vivo revealed by protein nitration and hydroxylation

Role of peroxynitrite in macrophage microbicidal mechanisms in vivo revealed by protein nitration and hydroxylation

Autor Linares, E. Google Scholar
Giorgio, S. Google Scholar
Mortara, R. A. Google Scholar
Santos, CXC Google Scholar
Yamada, A. T. Google Scholar
Augusto, O. Google Scholar
Instituição Universidade de São Paulo (USP)
Universidade Estadual de Campinas (UNICAMP)
Universidade Federal de São Paulo (UNIFESP)
Resumo The cytotoxins produced by phagocytic cells lacking peroxidases such as macrophages remain elusive. To elucidate macrophage microbicidal mechanisms in vivo, we compared the lesion tissue responses of resistant (C57B1/6) and susceptible (BALB/c) mice to Leishmania amazonensis infection. This comparison demonstrated that parasite control relied on lesion macrophage activation with inducible nitric oxide synthase expression (iNOS), nitric oxide synthesis, and extensive nitration of parasites inside macrophage phagolysosomes at an early infection stage. Nitration and iNOS expression were monitored by confocal microscopy; nitric oxide synthesis was monitored by EPR. the main macrophage nitrating agent was shown to be peroxynitrite derived because parasite nitration occurred in the virtual absence of polymorphonuclear cells (monitored as peroxidase activity) and was accompanied by protein hydroxylation (monitored as 3-hydroxytyrosine levels). in vitro studies confirmed that peroxynitrite is cytotoxic to parasites whereas nitric oxide is cytostatic. the results indicate that peroxynitrite is likely to be produced close to the parasites and most of it reacts with carbon dioxide to produce carbonate radical anion and nitrogen dioxide whose concerted action leads to parasite nitration. in parallel, some peroxynitrite decomposition to the hydroxyl radical should occur due to the detection of hydroxylated proteins in the healing tissues. Consequently, peroxynitrite and derived radicals are likely to be important macrophage-derived cytotoxins. (C) 2001 Elsevier Science Inc.
Assunto macrophage-derived cytotoxins
protein nitration and hydroxylation
nitric oxide
superoxide anion
carbonate radical anion
intracellular microorganisms
free radicals
Idioma Inglês
Data 2001-06-01
Publicado em Free Radical Biology and Medicine. Oxford: Pergamon-Elsevier B.V., v. 30, n. 11, p. 1234-1242, 2001.
ISSN 0891-5849 (Sherpa/Romeo, fator de impacto)
Editor Elsevier B.V.
Extensão 1234-1242
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000169177900004

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