Neutrophils and Neutrophil Extracellular Traps Regulate Immune Responses in Health and Disease

Mulay, Shrikant R.; Anders, Hans‐Joachim

doi:10.3390/cells9092130

Cited by 17 publications

(9 citation statements)

References 23 publications

(31 reference statements)

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“…Although NETs play a beneficial role in the defense of their host from pathogens, extended inflammation connected with their presence may cause a cascade of unfavorable reactions. The example of such reactions is the production of antibodies against the host’s DNA (autoimmunization), damage to surrounding tissue, or the occurrence of atherothrombotic events [ 3 , 4 , 7 , 20 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ].…”

Section: Neutrophil Extracellular Trapsmentioning

confidence: 99%

Significance of NETs Formation in COVID-19

Janiuk

Jabłońska

Garley

2021

Cells

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Severe contagious respiratory disease—COVID-19—caused by the SARS-CoV-2 coronavirus, can lead to fatal respiratory failure associated with an excessive inflammatory response. Infiltration and spread of SARS-CoV-2 are based on the interaction between the virus’ structural protein S and the cell’s receptor–angiotensin-converting enzyme 2 (ACE2), with the simultaneous involvement of human trans-membrane protease, serine 2 (TMPRSS2). Many scientific reports stress the importance of elevated recruitment and activity of neutrophils, which can form extracellular neutrophil traps (NETs) playing a significant role in the mechanism of combating pathogens, in the pathogenesis of COVID-19. Excessive generation of NETs during prolonged periods of inflammation predisposes for the occurrence of undesirable reactions including thromboembolic complications and damage to surrounding tissues and organs. Within the present manuscript, we draw attention to the impact of NET generation on the severe course of COVID-19 in patients with concurrent cardiovascular and metabolic diseases. Additionally, we indicate the necessity to explore not only the cellular but also the molecular bases of COVID-19 pathogenesis, which may aid the development of dedicated therapies meant to improve chances for the successful treatment of patients. We also present new directions of research into medications that display NETs formation regulatory properties as potential significant therapeutic strategies in the progress of COVID-19.

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Section: Neutrophil Extracellular Trapsmentioning

confidence: 99%

Significance of NETs Formation in COVID-19

Janiuk

Jabłońska

Garley

2021

Cells

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“…Initially, neutrophils and NETs were considered to be involved in antimicrobials, while a number of studies had shown that they also played a pivotal role in the development of sterile inflammation under several chronic inflammatory conditions [ 42 ]. Sterile inflammation occurs in the absence of microorganisms, and it can be induced by physical, chemical, metabolic, or antigenic stimuli.…”

Section: Neutrophils and Nets In Sterile Inflammationmentioning

confidence: 99%

An Update on the Pathogenic Role of Neutrophils in Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still’s Disease

Kim

Ahn

Jung

et al. 2021

IJMS

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Neutrophils are innate immune phagocytes that play a key role in immune defense against invading pathogens. The main offensive mechanisms of neutrophils are the phagocytosis of pathogens, release of granules, and production of cytokines. The formation of neutrophil extracellular traps (NETs) has been described as a novel defense mechanism in the literature. NETs are a network of fibers assembled from chromatin deoxyribonucleic acid, histones, and neutrophil granule proteins that have the ability to kill pathogens, while they can also cause toxic effects in hosts. Activated neutrophils with NET formation stimulate autoimmune responses related to a wide range of inflammatory autoimmune diseases by exposing autoantigens in susceptible individuals. The association between increased NET formation and autoimmunity was first reported in antineutrophil cytoplasmic antibody-related vasculitis, and the role of NETs in various diseases, including systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, has since been elucidated in research. Herein, we discuss the mechanistic role of neutrophils, including NETs, in the pathogenesis of systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still’s disease (AOSD), and provide their clinical values as biomarkers for monitoring and prognosis.

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“…NETs are involved in the development of autoimmunity by breaking down the self-tolerance of the immune system. They may also be potentially useful as markers in order to assess the development and prognosis of autoimmune diseases (7,8). The study by Bergqvist and co-workers showed that NETs were higher in dermal tissues in the early phases of ICmediated small vessel vasculitis in hypersensitivity vasculitis and IgAV (9).…”

Section: Introductionmentioning

confidence: 99%

The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis

Chen

Zou

et al. 2021

Front. Immunol.

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ObjectivesThis aim of this study was to determine whether neutrophil extracellular traps (NETs) are involved in the pathogenesis of IgA vasculitis (IgAV) and investigate whether the circulating NETs levels are associated with disease activity in children.MethodsWe performed a case-control study and collected blood samples from 193 children with different stages of IgAV (61 were at the onset stage, 64 at the remission stage, 43 at the active stage, and 25 were undergoing drug withdrawal). A total of 192 healthy children were recruited as controls. Circulating cell free DNA (cf-DNA) was obtained from the plasma and quantified by using the Quant-iT PicoGreen DNA quantification kit. NETs-associated myeloperoxidase-DNA (MPO-DNA), citrullinated-histone H3 (cit-H3), neutrophil elastase (NE), and the deoxyribonuclease I (DNase I) concentrations were measured using enzyme-linked immunosorbent assays. The presence of NETs in the kidney and gastrointestinal tissues of onset and active IgAV patients was determined by multiple immunofluorescence staining in 15 IgAV nephritis patients and 9 IgAV patients without IgAV nephritis, respectively. NETs degradation potency of collected sera samples from IgAV patients were checked in vitro. Relationships between circulating levels of cf-DNA with MPO-DNA, NE, and DNase I and the patients were analyzed.ResultsCirculating levels of cf-DNA in onset and active IgAV patients were significantly higher than those in remission and drug withdrawal patients as well as healthy controls. The results were similar for MPO-DNA and NE. The levels of circulating cf-DNA correlated significantly with MPO-DNA, NE and DNase I. A significantly decreased degradation of NETs from the onset and active IgAV patients was observed, but was normal in healthy controls. Furthermore, presence of NETs was also confirmed in all renal and gastrointestinal tissues obtained from the onset and active IgAV patients but not control samples.ConclusionsOur data showed that NETs were released into the circulation of IgAV patients and are involved in the disease activity. The circulating levels of NETs maybe used to assess disease severity in children with IgAV.

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Neutrophils and Neutrophil Extracellular Traps Regulate Immune Responses in Health and Disease

Abstract: Neutrophils are first responders of antimicrobial host defense and sterile inflammation, and therefore, play important roles during health and disease [...]

Cited by 17 publications

References 23 publications

Significance of NETs Formation in COVID-19

Significance of NETs Formation in COVID-19

An Update on the Pathogenic Role of Neutrophils in Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still’s Disease

The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis

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