SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology.
A549 Cells
Adult
Angiotensin-Converting Enzyme 2
Betacoronavirus
/ physiology
COVID-19
Cell Death
Coronavirus Infections
/ blood
Epithelial Cells
/ pathology
Extracellular Traps
/ physiology
Female
HeLa Cells
Humans
Male
Neutrophil Activation
Pandemics
Peptidyl-Dipeptidase A
/ metabolism
Pneumonia, Viral
/ blood
SARS-CoV-2
Serine Proteases
/ metabolism
Suction
Trachea
/ immunology
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
07 12 2020
07 12 2020
Historique:
received:
06
06
2020
revised:
11
08
2020
accepted:
31
08
2020
entrez:
14
9
2020
pubmed:
15
9
2020
medline:
30
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32926098
pii: 152086
doi: 10.1084/jem.20201129
pmc: PMC7488868
pii:
doi:
Substances chimiques
Serine Proteases
EC 3.4.-
Peptidyl-Dipeptidase A
EC 3.4.15.1
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2020 Veras et al.
Déclaration de conflit d'intérêts
Disclosures: The authors declare no competing interests exist.
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