The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19).

The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19).
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DOI:
10.1038/s41598-020-76781-0
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发表时间:
2020-11-12
期刊:
影响因子:
4.6
通讯作者:
Morrot A
Morrot A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Arcanjo A;Logullo J;Menezes CCB;de Souza Carvalho Giangiarulo TC;Dos Reis MC;de Castro GMM;da Silva Fontes Y;Todeschini AR;Freire-de-Lima L;Decoté-Ricardo D;Ferreira-Pereira A;Freire-de-Lima CG;Barroso SPC;Takiya C;Conceição-Silva F;Savino W;Morrot A

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新型冠状病毒SARS-CoV-2导致新冠肺炎,一种威胁数百万人的高致病性病毒感染。大多数感染者没有症状或症状轻微,表现出普通感冒的典型临床症状。然而,约20%的患者可进展为急性呼吸窘迫综合征(ARDS),约5%的患者可进展至死亡。最近,血管紧张素转换酶2(ACE2)被证明是病毒进入宿主靶细胞的功能受体。ACE2在合并症患者中的上调可能代表病毒载量增加和感染扩散到肺外组织的倾向。这种全身性感染与感染组织中较高的中性粒细胞/淋巴细胞比率和高水平的促炎细胞因子有关,导致广泛的微血栓形成并伴有多器官衰竭。在这里,我们研究了SARS-CoV-2是否能刺激细胞外中性粒细胞陷阱(Net),这一过程被称为NETsis。我们首次证明了SARS-CoV-2实际上能够激活人类中性粒细胞中的NETsis。我们的发现表明,这一过程与中性粒细胞内ROS水平的增加有关。ROS-Net途径在血栓形成中起作用,我们的研究表明这一靶点对于疾病治疗方法的重要性。
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.
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