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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.)

Neutrophil extracellular traps (NETs) exacerbate severity of infant sepsis

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Autor(es):
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Colon, David F. [1] ; Wanderley, Carlos W. [2] ; Franchin, Marcelo [3] ; Silva, Camila M. [2] ; Hiroki, Carlos H. [1] ; Castanheira, Fernanda V. S. [4] ; Donate, Paula B. [1] ; Lopes, Alexandre H. [4] ; Volpon, Leila C. [5] ; Kavaguti, Silvia K. [5] ; Borges, Vanessa F. [4] ; Speck-Hernandez, Cesar A. [1] ; Ramalho, Fernando [6] ; Carlotti, Ana P. [5] ; Carmona, Fabio [5] ; Alves-Filho, Jose C. [4] ; Liew, Foo Y. [7, 8] ; Cunha, Fernando Q. [4]
Número total de Autores: 18
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Fed Ceara, Dept Physiol & Pharmacol, BR-60020181 Fortaleza, CE - Brazil
[3] Univ Estadual Campinas, Dept Pharmacol, BR-13083970 Campinas, SP - Brazil
[4] Univ Sao Paulo, Dept Pharmacol, Sch Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil
[5] Univ Sao Paulo, Sch Med Ribeirao Preto, Pediat, BR-14049900 Ribeirao Preto, SP - Brazil
[6] Univ Sao Paulo, Dept Pathol, Sch Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil
[7] Soochow Univ, Sch Biol & Basic Med Sci, Suzhou 215006 - Peoples R China
[8] Univ Glasgow, Glasgow Biomed Res Ctr, Div Immunol Infect & Inflammat, Glasgow G12 8QQ, Lanark - Scotland
Número total de Afiliações: 8
Tipo de documento: Artigo Científico
Fonte: CRITICAL CARE; v. 23, APR 8 2019.
Citações Web of Science: 0
Resumo

BackgroundNeutrophil extracellular traps (NETs) are innate defense mechanisms that are also implicated in the pathogenesis of organ dysfunction. However, the role of NETs in pediatric sepsis is unknown.MethodsInfant (2weeks old) and adult (6weeks old) mice were submitted to sepsis by intraperitoneal (i.p.) injection of bacteria suspension or lipopolysaccharide (LPS). Neutrophil infiltration, bacteremia, organ injury, and concentrations of cytokine, NETs, and DNase in the plasma were measured. Production of reactive oxygen and nitrogen species and release of NETs by neutrophils were also evaluated. To investigate the functional role of NETs, mice undergoing sepsis were treated with antibiotic plus rhDNase and the survival, organ injury, and levels of inflammatory markers and NETs were determined. Blood samples from pediatric and adult sepsis patients were collected and the concentrations of NETs measured.ResultsInfant C57BL/6 mice subjected to sepsis or LPS-induced endotoxemia produced significantly higher levels of NETs than the adult mice. Moreover, compared to that of the adult mice, this outcome was accompanied by increased organ injury and production of inflammatory cytokines. The increased NETs were associated with elevated expression of Padi4 and histone H3 citrullination in the neutrophils. Furthermore, treatment of infant septic mice with rhDNase or a PAD-4 inhibitor markedly attenuated sepsis. Importantly, pediatric septic patients had high levels of NETs, and the severity of pediatric sepsis was positively correlated with the level of NETs.ConclusionThis study reveals a hitherto unrecognized mechanism of pediatric sepsis susceptibility and suggests that NETs represents a potential target to improve clinical outcomes of sepsis. (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