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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

THE ATYPICAL CHEMOKINE RECEPTOR ACKR2 IS PROTECTIVE AGAINST SEPSIS

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Autor(es):
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Silva Castanheira, Fernanda V. e [1] ; Borges, Vanessa [1] ; Sonego, Fabiane [1] ; Kanashiro, Alexandre [1] ; Donate, Paula B. [2] ; Melo, Paulo H. [2] ; Pallas, Kenneth [3] ; Russo, Remo C. [4] ; Amaral, Flavio A. [5] ; Teixeira, Mauro M. [5] ; Ramalho, Fernando S. [6] ; Cunha, Thiago M. [1] ; Liew, Foo Y. [7, 3] ; Alves-Filho, Jose C. [1] ; Graham, Gerard J. [3] ; Cunha, Fernando Q. [1]
Número total de Autores: 16
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto - Brazil
[3] Univ Glasgow, Inst Infect Immun & Inflammat, Glasgow, Lanark - Scotland
[4] Fed Univ Minas Gerais UFMG, Dept Physiol & Biophys, Lab Pulm Immunol & Mech, Belo Horizonte, MG - Brazil
[5] Fed Univ Minas Gerais UFMG, Dept Physiol & Biophys, Lab Immunopharmacol Biochem & Immunol, Belo Horizonte, MG - Brazil
[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol & Legal Med, Ribeirao Preto - Brazil
[7] Soochow Univ, Sch Biol & Basic Med Sci, Suzhou - Peoples R China
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: Shock; v. 49, n. 6, p. 682-689, JUN 2018.
Citações Web of Science: 3
Resumo

Sepsis is a systemic inflammatory response as a result of uncontrolled infections. Neutrophils are the first cells to reach the primary sites of infection, and chemokines play a key role in recruiting neutrophils. However, in sepsis chemokines could also contribute to neutrophil infiltration to vital organs leading to multiple organ failure. ACKR2 is an atypical chemokine receptor, which can remove and degrade inflammatory CC chemokines. The role of ACK2 in sepsis is unknown. Using a model of cecal ligation and puncture (CLP), we demonstrate here that ACKR2 deficient ((-/-)) mice exhibited a significant reduction in the survival rate compared with similarly treated wild-type (WT) mice. However, neutrophil migration to the peritoneal cavity and bacterial load were similar between WT and ACKR2(-/-) mice during CLP. In contrast, ACKR2(-/-) mice showed increased neutrophil infiltration and elevated CC chemokine levels in the lung, kidney, and heart compared with the WT mice. In addition, ACKR2(-/-) mice also showed more severe lesions in the lung and kidney than those in the WT mice. Consistent with these results, WT mice under nonsevere sepsis (90% survival) had higher expression of ACKR2 in these organs than mice under severe sepsis (no survival). Finally, the lungs from septic patients showed increased number of ACKR2 thorn cells compared with those of nonseptic patients. Our data indicate that ACKR2 may have a protective role during sepsis, and the absence of ACKR2 leads to exacerbated chemokine accumulation, neutrophil infiltration, and damage to vital organs. (AU)

Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
Beneficiário:Fernando de Queiroz Cunha
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 11/19670-0 - Mecanismos envolvidos na fisiopatologia da artrite reumatóide, dor e sepse
Beneficiário:Fernando de Queiroz Cunha
Linha de fomento: Auxílio à Pesquisa - Temático