Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide.
Autor(a) principal: | |
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Data de Publicação: | 2007 |
Outros Autores: | , , , , , , , , |
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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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:icict/10081Q0VTU8ODTyBOw4NPLUVYQ0xVU0lWQSBERSBESVJFSVRPUyBBVVRPUkFJUwoKQW8gYWNlaXRhciBvcyBURVJNT1MgZSBDT05EScOHw5VFUyBkZXN0YSBDRVNTw4NPLCBvIEFVVE9SIGUvb3UgVElUVUxBUiBkZSBkaXJlaXRvcyBhdXRvcmFpcyBzb2JyZSBhIE9CUkEgZGUgcXVlIHRyYXRhIGVzdGUgZG9jdW1lbnRvOgoKQ0VERSBlIFRSQU5TRkVSRSwgdG90YWwgZSBncmF0dWl0YW1lbnRlLCDDoCBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVosIGVtIGNhcsOhdGVyIHBlcm1hbmVudGUsIGlycmV2b2fDoXZlbCBlIE7Dg08gRVhDTFVTSVZPLCAKdG9kb3Mgb3MgZGlyZWl0b3MgcGF0cmltb25pYWlzIE7Dg08gQ09NRVJDSUFJUyBkZSB1dGlsaXphw6fDo28gZGEgT0JSQSBhcnTDrXN0aWNhIGUvb3UgY2llbnTDrWZpY2EgaW5kaWNhZGEgYWNpbWEsIGluY2x1c2l2ZSBvcyBkaXJlaXRvcyAKZGUgdm96IGUgaW1hZ2VtIHZpbmN1bGFkb3Mgw6AgT0JSQSwgZHVyYW50ZSB0b2RvIG8gcHJhem8gZGUgZHVyYcOnw6NvIGRvcyBkaXJlaXRvcyBhdXRvcmFpcywgZW0gcXVhbHF1ZXIgaWRpb21hIGUgZW0gdG9kb3Mgb3MgcGHDrXNlczsKICAgICAgICAKQUNFSVRBIHF1ZSBhIGNlc3PDo28gdG90YWwgbsOjbyBleGNsdXNpdmEsIHBlcm1hbmVudGUgZSBpcnJldm9nw6F2ZWwgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIHBhdHJpbW9uaWFpcyBuw6NvIGNvbWVyY2lhaXMgZGUgdXRpbGl6YcOnw6NvIApkZSBxdWUgdHJhdGEgZXN0ZSBkb2N1bWVudG8gaW5jbHVpLCBleGVtcGxpZmljYXRpdmFtZW50ZSwgb3MgZGlyZWl0b3MgZGUgZGlzcG9uaWJpbGl6YcOnw6NvIGUgY29tdW5pY2HDp8OjbyBww7pibGljYSBkYSBPQlJBLCBlbSBxdWFscXVlciAKbWVpbyBvdSB2ZcOtY3VsbywgaW5jbHVzaXZlIGVtIFJlcG9zaXTDs3Jpb3MgRGlnaXRhaXMsIGJlbSBjb21vIG9zIGRpcmVpdG9zIGRlIHJlcHJvZHXDp8OjbywgZXhpYmnDp8OjbywgZXhlY3XDp8OjbywgZGVjbGFtYcOnw6NvLCBleHBvc2nDp8OjbywgCmFycXVpdmFtZW50bywgaW5jbHVzw6NvIGVtIGJhbmNvIGRlIGRhZG9zLCBwcmVzZXJ2YcOnw6NvLCBkaWZ1c8OjbywgZGlzdHJpYnVpw6fDo28sIGRpdnVsZ2HDp8OjbywgZW1wcsOpc3RpbW8sIHRyYWR1w6fDo28sIGluY2x1c8OjbyBlbSBub3ZhcyAKb2JyYXMgb3UgY29sZXTDom5lYXMsIHJldXRpbGl6YcOnw6NvLCBlZGnDp8OjbywgcHJvZHXDp8OjbyBkZSBtYXRlcmlhbCBkaWTDoXRpY28gZSBjdXJzb3Mgb3UgcXVhbHF1ZXIgZm9ybWEgZGUgdXRpbGl6YcOnw6NvIG7Do28gY29tZXJjaWFsOwogICAgICAgIApSRUNPTkhFQ0UgcXVlIGEgY2Vzc8OjbyBhcXVpIGVzcGVjaWZpY2FkYSBjb25jZWRlIMOgIEZJT0NSVVogLSBGVU5EQcOHw4NPIE9TV0FMRE8gQ1JVWiBvIGRpcmVpdG8gZGUgYXV0b3JpemFyIHF1YWxxdWVyIHBlc3NvYSDigJMgZsOtc2ljYSAKb3UganVyw61kaWNhLCBww7pibGljYSBvdSBwcml2YWRhLCBuYWNpb25hbCBvdSBlc3RyYW5nZWlyYSDigJMgYSBhY2Vzc2FyIGUgdXRpbGl6YXIgYW1wbGFtZW50ZSBhIE9CUkEsIHNlbSBleGNsdXNpdmlkYWRlLCBwYXJhIHF1YWlzcXVlciAKZmluYWxpZGFkZXMgbsOjbyBjb21lcmNpYWlzOwogICAgICAgIApERUNMQVJBIHF1ZSBhIG9icmEgw6kgY3JpYcOnw6NvIG9yaWdpbmFsIGUgcXVlIMOpIG8gdGl0dWxhciBkb3MgZGlyZWl0b3MgYXF1aSBjZWRpZG9zIGUgYXV0b3JpemFkb3MsIHJlc3BvbnNhYmlsaXphbmRvLXNlIGludGVncmFsbWVudGUgCnBlbG8gY29udGXDumRvIGUgb3V0cm9zIGVsZW1lbnRvcyBxdWUgZmF6ZW0gcGFydGUgZGEgT0JSQSwgaW5jbHVzaXZlIG9zIGRpcmVpdG9zIGRlIHZveiBlIGltYWdlbSB2aW5jdWxhZG9zIMOgIE9CUkEsIG9icmlnYW5kby1zZSBhIAppbmRlbml6YXIgdGVyY2Vpcm9zIHBvciBkYW5vcywgYmVtIGNvbW8gaW5kZW5pemFyIGUgcmVzc2FyY2lyIGEgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaIGRlIGV2ZW50dWFpcyBkZXNwZXNhcyBxdWUgdmllcmVtIGEgCnN1cG9ydGFyLCBlbSByYXrDo28gZGUgcXVhbHF1ZXIgb2ZlbnNhIGEgZGlyZWl0b3MgYXV0b3JhaXMgb3UgZGlyZWl0b3MgZGUgdm96IG91IGltYWdlbSwgcHJpbmNpcGFsbWVudGUgbm8gcXVlIGRpeiByZXNwZWl0byBhIHBsw6FnaW8gCmUgdmlvbGHDp8O1ZXMgZGUgZGlyZWl0b3M7CiAgICAgICAgCkFGSVJNQSBxdWUgY29uaGVjZSBhIFBvbMOtdGljYSBJbnN0aXR1Y2lvbmFsIGRlIEFjZXNzbyBBYmVydG8gZGEgSW5zdGl0dWnDp8OjbyBlIGFzIGRpcmV0cml6ZXMgcGFyYSBvIGZ1bmNpb25hbWVudG8gZG8gcmVwb3NpdMOzcmlvIAppbnN0aXR1Y2lvbmFsIEFSQ0EKRepositório 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 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
American Thoracic Society |
publisher.none.fl_str_mv |
American Thoracic Society |
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reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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FIOCRUZ |
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