Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide.

Detalhes bibliográficos
Autor(a) principal: Santos, Fabrício Rios
Data de Publicação: 2007
Outros Autores: Alves Filho, José Carlos Farias, Souto, Fabrício Oliveira, Spiller, Fernando, Freitas, Andressa, Lotufo, Celina Monteiro da Cruz, Soares, Milena Botelho Pereira, Santos, Ricardo Ribeiro dos, Teixeira, Mauro Martins, Cunha, Fernando Queiroz
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/10081
Resumo: Universidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil / University of Santa Cruz. Department of Health. Santa Cruz, BA, Brasil
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spelling Santos, Fabrício RiosAlves Filho, José Carlos FariasSouto, Fabrício OliveiraSpiller, FernandoFreitas, AndressaLotufo, Celina Monteiro da CruzSoares, Milena Botelho PereiraSantos, Ricardo Ribeiro dosTeixeira, Mauro MartinsCunha, Fernando Queiroz2015-04-17T18:40:45Z2015-04-17T18:40:45Z2007SANTOS, F. R. et al. Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide. American Journal of Respiratory and Critical Care Medicine, v. 175, n. 5, p. 490-497, 2007.1073-449Xhttps://www.arca.fiocruz.br/handle/icict/1008110.1164/rccm.200601-103OCengAmerican Thoracic SocietyDown-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil / University of Santa Cruz. Department of Health. Santa Cruz, BA, BrasilUniversidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, BrasilUniversity of Santa Cruz. Department of Health. Santa Cruz, BA, BrasilUniversidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, BrasilUniversidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, BrasilUniversidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratorio de Engenharia Tecidual e Imunofarmacologia . Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratorio de Engenharia Tecidual e Imunofarmacologia . Salvador, BA, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrasilUniversidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, BrasilRATIONALE: The failure of neutrophils to migrate to an infection focus during severe sepsis is an important determinant of the inability of a host to deal with an infectious insult. Our laboratory has shown that inducible nitric oxide synthase (iNOS) induction and NO production contribute to the failure of neutrophils to migrate in the context of sepsis. OBJECTIVES AND METHODS: We investigated whether CXCR2 expression contributed to the failure of neutrophils to migrate during severe sepsis and the role of NO in modulating CXCR2 expression on neutrophils in mice subjected to nonsevere (NS) or severe (S) cecal ligation and puncture (CLP). RESULTS: Neutrophil migration to the infection focus was deficient in S-CLP mice, a phenomenon prevented by pharmacologic (aminoguanidine, l-canavanine) or genetic (iNOS gene deletion) inhibition of iNOS. The expression of CXCR2 on neutrophils from S-CLP mice was significantly reduced when compared with neutrophils from NS-CLP or sham-operated mice. CXCR2 expression was reestablished by pharmacologic and genetic inhibition of iNOS. Immunofluorescence and confocal analysis revealed that iNOS blockade reduced neutrophil CXCR2 internalization. Adhesion and emigration of neutrophils in macrophage inflammatory protein-2-stimulated mesentery microcirculation were reduced in S-CLP mice, compared with NS-CLP mice, and reestablished by pretreatment with aminoguanidine or l-canavanine. The NO donor S-nitroso-N-acetyl-d,l-penicillamine inhibited CXCL8-induced human neutrophil chemotaxis and CXCR2 expression on human and murine neutrophils. CONCLUSION: These results highlight evidences that the failure of neutrophils to migrate to an infection focus during severe sepsis is associated with excessive NO production and NO-dependent regulation of the expression of CXCR2 on the neutrophil surfaceSepsisNeutrophil migrationCXCR2Nitric oxideRegulação para BaixoNeutrófilos/metabolismoÓxido Nítrico Sintase Tipo II/metabolismoÓxido Nítrico/metabolismoReceptores de Interleucina-8B/genéticaSepse/metabolismoAnimaisMovimento CelularQuimiotaxia de LeucócitoModelos Animais de DoençasCitometria de FluxoMasculinoCamundongosCamundongos Endogâmicos C57BLSepse/genéticaÍndice de Gravidade de Doençainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82352https://www.arca.fiocruz.br/bitstream/icict/10081/1/license.txtafbdf7d7a9bcf771a1cc7edf5f618413MD51ORIGINALSantos FR Down-regulation of....pdfSantos FR Down-regulation of....pdfapplication/pdf1145084https://www.arca.fiocruz.br/bitstream/icict/10081/2/Santos%20FR%20Down-regulation%20of....pdf28d28253aec81401016829d03b4d7378MD52TEXTSantos FR Down-regulation of....pdf.txtSantos FR Down-regulation of....pdf.txtExtracted texttext/plain47288https://www.arca.fiocruz.br/bitstream/icict/10081/3/Santos%20FR%20Down-regulation%20of....pdf.txt6c4a112606189fc1319fc4d273154595MD53icict/100812023-03-15 14:33:25.076oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:25Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide.
title Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide.
spellingShingle Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide.
Santos, Fabrício Rios
Sepsis
Neutrophil migration
CXCR2
Nitric oxide
Regulação para Baixo
Neutrófilos/metabolismo
Óxido Nítrico Sintase Tipo II/metabolismo
Óxido Nítrico/metabolismo
Receptores de Interleucina-8B/genética
Sepse/metabolismo
Animais
Movimento Celular
Quimiotaxia de Leucócito
Modelos Animais de Doenças
Citometria de Fluxo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Sepse/genética
Índice de Gravidade de Doença
title_short Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide.
title_full Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide.
title_fullStr Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide.
title_full_unstemmed Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide.
title_sort Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide.
author Santos, Fabrício Rios
author_facet Santos, Fabrício Rios
Alves Filho, José Carlos Farias
Souto, Fabrício Oliveira
Spiller, Fernando
Freitas, Andressa
Lotufo, Celina Monteiro da Cruz
Soares, Milena Botelho Pereira
Santos, Ricardo Ribeiro dos
Teixeira, Mauro Martins
Cunha, Fernando Queiroz
author_role author
author2 Alves Filho, José Carlos Farias
Souto, Fabrício Oliveira
Spiller, Fernando
Freitas, Andressa
Lotufo, Celina Monteiro da Cruz
Soares, Milena Botelho Pereira
Santos, Ricardo Ribeiro dos
Teixeira, Mauro Martins
Cunha, Fernando Queiroz
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Santos, Fabrício Rios
Alves Filho, José Carlos Farias
Souto, Fabrício Oliveira
Spiller, Fernando
Freitas, Andressa
Lotufo, Celina Monteiro da Cruz
Soares, Milena Botelho Pereira
Santos, Ricardo Ribeiro dos
Teixeira, Mauro Martins
Cunha, Fernando Queiroz
dc.subject.en.pt_BR.fl_str_mv Sepsis
Neutrophil migration
CXCR2
Nitric oxide
topic Sepsis
Neutrophil migration
CXCR2
Nitric oxide
Regulação para Baixo
Neutrófilos/metabolismo
Óxido Nítrico Sintase Tipo II/metabolismo
Óxido Nítrico/metabolismo
Receptores de Interleucina-8B/genética
Sepse/metabolismo
Animais
Movimento Celular
Quimiotaxia de Leucócito
Modelos Animais de Doenças
Citometria de Fluxo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Sepse/genética
Índice de Gravidade de Doença
dc.subject.decs.pt_BR.fl_str_mv Regulação para Baixo
Neutrófilos/metabolismo
Óxido Nítrico Sintase Tipo II/metabolismo
Óxido Nítrico/metabolismo
Receptores de Interleucina-8B/genética
Sepse/metabolismo
Animais
Movimento Celular
Quimiotaxia de Leucócito
Modelos Animais de Doenças
Citometria de Fluxo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Sepse/genética
Índice de Gravidade de Doença
description Universidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil / University of Santa Cruz. Department of Health. Santa Cruz, BA, Brasil
publishDate 2007
dc.date.issued.fl_str_mv 2007
dc.date.accessioned.fl_str_mv 2015-04-17T18:40:45Z
dc.date.available.fl_str_mv 2015-04-17T18:40:45Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SANTOS, F. R. et al. Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide. American Journal of Respiratory and Critical Care Medicine, v. 175, n. 5, p. 490-497, 2007.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/10081
dc.identifier.issn.none.fl_str_mv 1073-449X
dc.identifier.doi.none.fl_str_mv 10.1164/rccm.200601-103OC
identifier_str_mv SANTOS, F. R. et al. Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide. American Journal of Respiratory and Critical Care Medicine, v. 175, n. 5, p. 490-497, 2007.
1073-449X
10.1164/rccm.200601-103OC
url https://www.arca.fiocruz.br/handle/icict/10081
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Thoracic Society
publisher.none.fl_str_mv American Thoracic Society
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
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instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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