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

dc.creatorLinares, E
dc.creatorGiorgio, S
dc.creatorMortara, RA
dc.creatorSantos, CXC
dc.creatorYamada, AT
dc.creatorAugusto, O
dc.date2001
dc.date37043
dc.date2014-11-17T08:12:55Z
dc.date2015-11-26T17:15:21Z
dc.date2014-11-17T08:12:55Z
dc.date2015-11-26T17:15:21Z
dc.date.accessioned2018-03-29T00:03:36Z
dc.date.available2018-03-29T00:03:36Z
dc.identifierFree Radical Biology And Medicine. Pergamon-elsevier Science Ltd, v. 30, n. 11, n. 1234, n. 1242, 2001.
dc.identifier0891-5849
dc.identifierWOS:000169177900004
dc.identifier10.1016/S0891-5849(01)00516-0
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/79864
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/79864
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/79864
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1282028
dc.descriptionThe 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.
dc.description30
dc.description11
dc.description1234
dc.description1242
dc.languageen
dc.publisherPergamon-elsevier Science Ltd
dc.publisherOxford
dc.publisherInglaterra
dc.relationFree Radical Biology And Medicine
dc.relationFree Radic. Biol. Med.
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectmacrophage-derived cytotoxins
dc.subjectperoxynitrite
dc.subjectprotein nitration and hydroxylation
dc.subjectnitric oxide
dc.subjectsuperoxide anion
dc.subjectcarbonate radical anion
dc.subjectintracellular microorganisms
dc.subjectLeishmania
dc.subjectfree radicals
dc.subjectNitric-oxide Synthase
dc.subjectCarbonate Radical-anion
dc.subjectIn-vivo
dc.subjectMurine Leishmaniasis
dc.subjectTyrosine Nitration
dc.subjectActivated Macrophages
dc.subjectCatalyzed Oxidation
dc.subjectTrypanosoma-cruzi
dc.subjectReactive Nitrogen
dc.subjectDioxide
dc.titleRole of peroxynitrite in macrophage microbicidal mechanisms in vivo revealed by protein nitration and hydroxylation
dc.typeArtículos de revistas


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