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SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology.
Veras, Flavio Protasio; Pontelli, Marjorie Cornejo; Silva, Camila Meirelles; Toller-Kawahisa, Juliana E; de Lima, Mikhael; Nascimento, Daniele Carvalho; Schneider, Ayda Henriques; Caetité, Diego; Tavares, Lucas Alves; Paiva, Isadora M; Rosales, Roberta; Colón, David; Martins, Ronaldo; Castro, Italo Araujo; Almeida, Glaucia M; Lopes, Maria Isabel Fernandes; Benatti, Maíra Nilson; Bonjorno, Letícia Pastorelli; Giannini, Marcela Cavichioli; Luppino-Assad, Rodrigo; Almeida, Sérgio Luna; Vilar, Fernando; Santana, Rodrigo; Bollela, Valdes R; Auxiliadora-Martins, Maria; Borges, Marcos; Miranda, Carlos Henrique; Pazin-Filho, Antônio; da Silva, Luis Lamberti P; Cunha, Larissa Dias; Zamboni, Dario S; Dal-Pizzol, Felipe; Leiria, Luiz O; Siyuan, Li; Batah, Sabrina; Fabro, Alexandre; Mauad, Thais; Dolhnikoff, Marisa; Duarte-Neto, Amaro; Saldiva, Paulo; Cunha, Thiago Mattar; Alves-Filho, José Carlos; Arruda, Eurico; Louzada-Junior, Paulo; Oliveira, Renê Donizeti; Cunha, Fernando Queiroz.
Afiliação
  • Veras FP; Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Pontelli MC; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Silva CM; Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Toller-Kawahisa JE; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • de Lima M; Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Nascimento DC; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Schneider AH; Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Caetité D; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Tavares LA; Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Paiva IM; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Rosales R; Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Colón D; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Martins R; Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Castro IA; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Almeida GM; Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Lopes MIF; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Benatti MN; Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Bonjorno LP; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Giannini MC; Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Luppino-Assad R; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Almeida SL; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Vilar F; Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Santana R; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Bollela VR; Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Auxiliadora-Martins M; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Borges M; Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Miranda CH; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Pazin-Filho A; Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • da Silva LLP; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Cunha LD; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Zamboni DS; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Dal-Pizzol F; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Leiria LO; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Siyuan L; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Batah S; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Fabro A; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Mauad T; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Dolhnikoff M; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Duarte-Neto A; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Saldiva P; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Cunha TM; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Alves-Filho JC; Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Arruda E; Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Louzada-Junior P; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Oliveira RD; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Cunha FQ; Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
J Exp Med ; 217(12)2020 12 07.
Article em En | MEDLINE | ID: mdl-32926098
Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2-activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pneumonia Viral / Infecções por Coronavirus / Armadilhas Extracelulares / Betacoronavirus Limite: Adult / Female / Humans / Male Idioma: En Revista: J Exp Med Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pneumonia Viral / Infecções por Coronavirus / Armadilhas Extracelulares / Betacoronavirus Limite: Adult / Female / Humans / Male Idioma: En Revista: J Exp Med Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil