SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology

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 investigate...

Descripción completa

Detalles Bibliográficos
Autores principales: 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, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
Brief Definitive Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488868/
https://www.ncbi.nlm.nih.gov/pubmed/32926098
http://dx.doi.org/10.1084/jem.20201129
Descripción
Sumario: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.

Ejemplares similares