Is digital necrosis in COVID-19 caused by neutrophil extracellular traps: potential therapeutic strategies

Although neutrophil extracellular traps (NETs) were discovered only 16 years ago, they have already taken us from heaven to hell as we learned that apart from beneficial trapping of pathogens, they cause, or contribute to, numerous disorders. The latter is connected to their persistent presence in the blood or tissue, and we hardly know how they are removed in mild pathophysiological conditions and why their removal is impaired in multiple severe pathological conditions. Herein, we bring together all data available up till now on how NETs are cleared—from engaged cells, their phenotypes, to involved enzymes and molecules. Moreover, we hypothesize on why NET removal is challenged in multiple disorders and propose further directions for studies on NET removal as well as possible therapeutic strategies to have them cleared.

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NETs and oncologic process

Obstetrics Gynecology and Reproduction ◽

10.17749/2313-7347/ob.gyn.rep.2021.204 ◽

2021 ◽

Vol 15 (1) ◽

pp. 107-116

Author(s):

E. V. Slukhanchuk

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Neutrophil Extracellular Traps ◽

Therapeutic Strategies ◽

Innate Immune ◽

Systemic Lupus ◽

Extracellular Traps ◽

Activated Neutrophils ◽

Autoimmune Conditions

Neutrophil Extracellular Traps (NETs) represent the networks consisting of DNA, histones, and proteins produced by activated neutrophils. Such structures have been proved to play a crucial role in inducing neutrophil innate immune response in the pathogenesis of such autoimmune conditions as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, as well as in the pathogenesis of other non-infectious processes, e. g., clotting disorders, thrombosis, diabetes, atherosclerosis, vasculitis and oncology diseases. Recent studies on animal models and human pathologies have uncovered a tremendous role for NETs in tumor progression and metastasis. In this regard, NETs should be considered as pro-oncogenic substances, which further investigation will provide an opportunity to develop new therapeutic strategies.

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Neutrophils and Neutrophil Extracellular Traps Drive Necroinflammation in COVID-19

Cells ◽

10.3390/cells9061383 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1383 ◽

Cited By ~ 29

Author(s):

Bhawna Tomar ◽

Hans-Joachim Anders ◽

Jyaysi Desai ◽

Shrikant R. Mulay

Keyword(s):

Distress Syndrome ◽

Neutrophil Infiltration ◽

Neutrophil Extracellular Traps ◽

Therapeutic Strategies ◽

The Novel ◽

Extracellular Traps ◽

Putative Target ◽

Novel Therapeutic Strategies ◽

Novel Therapeutic

The COVID-19 pandemic is progressing worldwide with an alarming death toll. There is an urgent need for novel therapeutic strategies to combat potentially fatal complications. Distinctive clinical features of severe COVID-19 include acute respiratory distress syndrome, neutrophilia, and cytokine storm, along with severe inflammatory response syndrome or sepsis. Here, we propose the putative role of enhanced neutrophil infiltration and the release of neutrophil extracellular traps, complement activation and vascular thrombosis during necroinflammation in COVID-19. Furthermore, we discuss how neutrophilic inflammation contributes to the higher mortality of COVID-19 in patients with underlying co-morbidities such as diabetes and cardiovascular diseases. This perspective highlights neutrophils as a putative target for the immunopathologic complications of severely ill COVID-19 patients. Development of the novel therapeutic strategies targeting neutrophils may help reduce the overall disease fatality rate of COVID-19.

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