tetano
Editor, Senior Moderator
Sci Rep
. 2020 Nov 12;10(1):19630.
doi: 10.1038/s41598-020-76781-0.
The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19)
Ang?lica Arcanjo[SUP] 1 [/SUP], Jorgete Logullo[SUP] 2 [/SUP], Camilla Cristie Barreto Menezes[SUP] 3 [/SUP], Thais Chrispim de Souza Carvalho Giangiarulo[SUP] 4 [/SUP], Mirella Carneiro Dos Reis[SUP] 5 [/SUP], Gabriellen Menezes Migliani de Castro[SUP] 6 [/SUP], Yasmin da Silva Fontes[SUP] 6 [/SUP], Adriane Regina Todeschini[SUP] 2 [/SUP], Leonardo Freire-de-Lima[SUP] 2 [/SUP], Debora Decot?-Ricardo[SUP] 7 [/SUP], Ant?nio Ferreira-Pereira[SUP] 6 [/SUP], Celio Geraldo Freire-de-Lima[SUP] 2 [/SUP], Shana Priscila Coutinho Barroso[SUP] 4 [/SUP], Christina Takiya[SUP] 2 [/SUP], F?tima Concei??o-Silva[SUP] 8 [/SUP], Wilson Savino[SUP] 9 10 11 [/SUP], Alexandre Morrot[SUP] 12 13 [/SUP]
Affiliations
Abstract
The novel coronavirus SARS-CoV-2 causes COVID-19, a highly pathogenic viral infection threatening millions. The majority of the individuals infected are asymptomatic or mildly symptomatic showing typical clinical signs of common cold. However, approximately 20% of the patients can progress to acute respiratory distress syndrome (ARDS), evolving to death in about 5% of cases. Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for virus entry into host target cells. The upregulation of ACE2 in patients with comorbidities may represent a propensity for increased viral load and spreading of infection to extrapulmonary tissues. This systemic infection is associated with higher neutrophil to lymphocyte ratio in infected tissues and high levels of pro-inflammatory cytokines leading to an extensive microthrombus formation with multiorgan failure. Herein we investigated whether SARS-CoV-2 can stimulate extracellular neutrophils traps (NETs) in a process called NETosis. We demonstrated for the first time that SARS-CoV-2 in fact is able to activate NETosis in human neutrophils. Our findings indicated that this process is associated with increased levels of intracellular Reactive Oxygen Species (ROS) in neutrophils. The ROS-NET pathway plays a role in thrombosis formation and our study suggest the importance of this target for therapy approaches against disease.
. 2020 Nov 12;10(1):19630.
doi: 10.1038/s41598-020-76781-0.
The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19)
Ang?lica Arcanjo[SUP] 1 [/SUP], Jorgete Logullo[SUP] 2 [/SUP], Camilla Cristie Barreto Menezes[SUP] 3 [/SUP], Thais Chrispim de Souza Carvalho Giangiarulo[SUP] 4 [/SUP], Mirella Carneiro Dos Reis[SUP] 5 [/SUP], Gabriellen Menezes Migliani de Castro[SUP] 6 [/SUP], Yasmin da Silva Fontes[SUP] 6 [/SUP], Adriane Regina Todeschini[SUP] 2 [/SUP], Leonardo Freire-de-Lima[SUP] 2 [/SUP], Debora Decot?-Ricardo[SUP] 7 [/SUP], Ant?nio Ferreira-Pereira[SUP] 6 [/SUP], Celio Geraldo Freire-de-Lima[SUP] 2 [/SUP], Shana Priscila Coutinho Barroso[SUP] 4 [/SUP], Christina Takiya[SUP] 2 [/SUP], F?tima Concei??o-Silva[SUP] 8 [/SUP], Wilson Savino[SUP] 9 10 11 [/SUP], Alexandre Morrot[SUP] 12 13 [/SUP]
Affiliations
- PMID: 33184506
- DOI: 10.1038/s41598-020-76781-0
Abstract
The novel coronavirus SARS-CoV-2 causes COVID-19, a highly pathogenic viral infection threatening millions. The majority of the individuals infected are asymptomatic or mildly symptomatic showing typical clinical signs of common cold. However, approximately 20% of the patients can progress to acute respiratory distress syndrome (ARDS), evolving to death in about 5% of cases. Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for virus entry into host target cells. The upregulation of ACE2 in patients with comorbidities may represent a propensity for increased viral load and spreading of infection to extrapulmonary tissues. This systemic infection is associated with higher neutrophil to lymphocyte ratio in infected tissues and high levels of pro-inflammatory cytokines leading to an extensive microthrombus formation with multiorgan failure. Herein we investigated whether SARS-CoV-2 can stimulate extracellular neutrophils traps (NETs) in a process called NETosis. We demonstrated for the first time that SARS-CoV-2 in fact is able to activate NETosis in human neutrophils. Our findings indicated that this process is associated with increased levels of intracellular Reactive Oxygen Species (ROS) in neutrophils. The ROS-NET pathway plays a role in thrombosis formation and our study suggest the importance of this target for therapy approaches against disease.