Author | Santos, Fabrício Rios | |
Author | Alves Filho, José Carlos Farias | |
Author | Souto, Fabrício Oliveira | |
Author | Spiller, Fernando | |
Author | Freitas, Andressa | |
Author | Lotufo, Celina Monteiro da Cruz | |
Author | Soares, Milena Botelho Pereira | |
Author | Santos, Ricardo Ribeiro dos | |
Author | Teixeira, Mauro Martins | |
Author | Cunha, Fernando Queiroz | |
Access date | 2015-04-17T18:40:45Z | |
Available date | 2015-04-17T18:40:45Z | |
Document date | 2007 | |
Citation | 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. | pt_BR |
ISSN | 1073-449X | |
URI | https://www.arca.fiocruz.br/handle/icict/10081 | |
Language | eng | pt_BR |
Publisher | American Thoracic Society | pt_BR |
Rights | open access | pt_BR |
Title | Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide. | pt_BR |
Type | Article | pt_BR |
DOI | 10.1164/rccm.200601-103OC | |
Abstract | RATIONALE: 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 surface | pt_BR |
Affilliation | 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 | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil | pt_BR |
Affilliation | University of Santa Cruz. Department of Health. Santa Cruz, BA, Brasil | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratorio de Engenharia Tecidual e Imunofarmacologia . Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratorio de Engenharia Tecidual e Imunofarmacologia . Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil | pt_BR |
Subject | Sepsis | pt_BR |
Subject | Neutrophil migration | pt_BR |
Subject | CXCR2 | pt_BR |
Subject | Nitric oxide | pt_BR |
DeCS | Regulação para Baixo | pt_BR |
DeCS | Neutrófilos/metabolismo | pt_BR |
DeCS | Óxido Nítrico Sintase Tipo II/metabolismo | pt_BR |
DeCS | Óxido Nítrico/metabolismo | pt_BR |
DeCS | Receptores de Interleucina-8B/genética | pt_BR |
DeCS | Sepse/metabolismo | pt_BR |
DeCS | Animais | pt_BR |
DeCS | Movimento Celular | pt_BR |
DeCS | Quimiotaxia de Leucócito | pt_BR |
DeCS | Modelos Animais de Doenças | pt_BR |
DeCS | Citometria de Fluxo | pt_BR |
DeCS | Masculino | pt_BR |
DeCS | Camundongos | pt_BR |
DeCS | Camundongos Endogâmicos C57BL | pt_BR |
DeCS | Sepse/genética | pt_BR |
DeCS | Índice de Gravidade de Doença | pt_BR |