Neutrophil Extracellular Traps (NETs) and Covid-19: A new frontiers for therapeutic modality

被引:147
作者
Al-Kuraishy, Hayder M. [1 ]
Al-Gareeb, Ali I. [1 ]
Al-hussaniy, Hany Akeel [2 ]
Al-Harcan, Nasser A. Hadi [3 ]
Alexiou, Athanasios [4 ,5 ]
Batiha, Gaber El-Saber [6 ]
机构
[1] Al Mustansiriyiah Univ, Dept Clin Pharmacol & Med, Coll Med, Baghdad, Iraq
[2] Al Nukhaba Univ Baghdad, Dept Pharmacol, Coll Anesthet, Baghdad, Iraq
[3] Al Rasheed Univ Coll, Dept Clin Pharmacol & Med, Coll Med, Baghdad, Iraq
[4] Novel Global Community Educ Fdn, Dept Sci & Engn, Hebersham, Australia
[5] AFNP Med Austria, Vienna, Austria
[6] Damanhour Univ, Dept Pharmacol & Therapeut, Fac Vet Med, Damanhour 22511, Al Beheira, Egypt
关键词
Covid-19; Neutrophil extracellular traps; Cytokine storm; Immuno-thrombosis; Acute lung injury; Acute respiratory distress syndrome; DIPHENYLENEIODONIUM CHLORIDE; LUNG INJURY; HYDROXYCHLOROQUINE; PLATELET; COMBINATION; SIVELESTAT; ACTIVATION; THROMBOSIS; INHIBITION; COAGULATION;
D O I
10.1016/j.intimp.2021.108516
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Coronavirus disease 2019 (Covid-19) is a worldwide infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). In severe SARS-CoV-2 infection, there is severe inflammatory reactions due to neutrophil recruitments and infiltration in the different organs with the formation of neutrophil extracellular traps (NETs), which involved various complications of SARS-CoV-2 infection. Therefore, the objective of the present review was to explore the potential role of NETs in the pathogenesis of SARS-CoV-2 infection and to identify the targeting drugs against NETs in Covid-19 patients. Different enzyme types are involved in the formation of NETs, such as neutrophil elastase (NE), which degrades nuclear protein and release histones, peptidyl arginine deiminase type 4 (PADA4), which releases chromosomal DNA and gasdermin D, which creates pores in the NTs cell membrane that facilitating expulsion of NT contents. Despite of the beneficial effects of NETs in controlling of invading pathogens, sustained formations of NETs during respiratory viral infections are associated with collateral tissue injury. Excessive development of NETs in SARS-CoV-2 infection is linked with the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) due to creation of the NETs-IL1 beta loop. Also, aberrant NTs activation alone or through NETs formation may augment SARS-CoV-2-induced cytokine storm (CS) and macrophage activation syndrome (MAS) in patients with severe Covid-19. Furthermore, NETs formation in SARS-CoV-2 infection is associated with immuno-thrombosis and the development of ALI/ARDS. Therefore, anti-NETs therapy of natural or synthetic sources may mitigate SARS-CoV-2 infection induced exaggerated immune response, hyperinflammation, immuno-thrombosis, and other complications.
引用
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页数:14
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