Extracellular traps in kidney disease

Nakazawa, Daigo; Marschner, Julian A.; Platen, Louise; Anders, Hans‐Joachim

doi:10.1016/j.kint.2018.08.035

Cited by 70 publications

(63 citation statements)

References 157 publications

(162 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role of nucleosome in autoimmune diseases was demonstrated, as well as histones antimicrobial activity, yet can also cause tissue damage and other pathological abnormalities. Thus, histones released from NETs are, by themselves, unique cytotoxic DAMPs linking cell necrosis and inflammation (as reviewed by Nakasawa et al, 2018 [21]).…”

Section: Nuclear Dnamentioning

confidence: 99%

See 1 more Smart Citation

Neutrophil Extracellular Traps and By-Products Play a Key Role in COVID-19: Pathogenesis, Risk Factors, and Therapy

Thierry

Roch

2020

JCM

106

135

View full text Add to dashboard Cite

Understanding of the pathogenesis of the coronavirus disease-2019 (COVID-19) remains incomplete, particularly in respect to the multi-organ dysfunction it may cause. We were the first to report the analogous biological and physiological features of COVID-19 pathogenesis and the harmful amplification loop between inflammation and tissue damage induced by the dysregulation of neutrophil extracellular traps (NETs) formation. Given the rapid evolution of this disease, the nature of its symptoms, and its potential lethality, we hypothesize that COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. Here, we describe in-depth the correlations of COVID-19 symptoms and biological features with those where uncontrolled NET formation is implicated in various sterile or infectious diseases. General clinical conditions, as well as numerous pathological and biological features, are analogous with NETs deleterious effects. Among NETs by-products implicated in COVID-19 pathogenesis, one of the most significant appears to be elastase, in accelerating virus entry and inducing hypertension, thrombosis and vasculitis. We postulate that severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) may evade innate immune response, causing uncontrolled NETs formation and multi-organ failure. In addition, we point to indicators that NETS-associated diseases are COVID-19 risk factors. Acknowledging that neutrophils are the principal origin of extracellular and circulating DNA release, we nonetheless, explain why targeting NETs rather than neutrophils themselves may in practice be a better strategy. This paper also offers an in-depth review of NET formation, function and pathogenic dysregulation, as well as of current and prospective future therapies to control NETopathies. As such, it enables us also to suggest new therapeutic strategies to fight COVID-19. In combination with or independent of the latest tested approaches, we propose the evaluation, in the short term, of treatments with DNase-1, with the anti-diabetic Metformin, or with drugs targeting elastase (i.e., Silvelestat). With a longer perspective, we also advocate a significant increase in research on the development of toll-like receptors (TLR) and C-type lectin-like receptors (CLEC) inhibitors, NET-inhibitory peptides, and on anti-IL-26 therapies.

show abstract

Section: Nuclear Dnamentioning

confidence: 99%

“…The formation of NETS has also been observed in pathologies such as painful sickle cell crisis, periodontitis, transfusion-related ALI, Felty syndrome, liver diseases (alcohol-associated liver disease and portal hypertension), kidney diseases [21], in severe obesity [57], and in neuropathologies [61] (Table 1).…”

Section: Other Pathologiesmentioning

confidence: 99%

Neutrophil Extracellular Traps and By-Products Play a Key Role in COVID-19: Pathogenesis, Risk Factors, and Therapy

Thierry

Roch

2020

JCM

106

135

View full text Add to dashboard Cite

show abstract

“…The Janus kinase (JAK) family (JAK1, JAK2, JAK3, and TYK2) and signal transducer and activator of transcription (STAT) family (STAT1-STAT4, STAT5A, STAT5B, and STAT6) [93,94] transduce signals for numerous growth factors and cytokines, including families of interferon (IFN), gp130, and γC in an isoform-specific manner [95]. Upon ligand binding, JAK phosphorylates the cytokine receptor via the tyrosine residues of the cytoplasmic domain, which in turn recruits and activates STAT for nuclear translocation to bind on their target genes.…”

Section: Jak/stat Signalingmentioning

confidence: 99%

The Emerging Role of Innate Immunity in Chronic Kidney Diseases

Tang

Zhang

Chan

et al. 2020

IJMS

View full text Add to dashboard Cite

Renal fibrosis is a common fate of chronic kidney diseases. Emerging studies suggest that unsolved inflammation will progressively transit into tissue fibrosis that finally results in an irreversible end-stage renal disease (ESRD). Renal inflammation recruits and activates immunocytes, which largely promotes tissue scarring of the diseased kidney. Importantly, studies have suggested a crucial role of innate immunity in the pathologic basis of kidney diseases. This review provides an update of both clinical and experimental information, focused on how innate immune signaling contributes to renal fibrogenesis. A better understanding of the underlying mechanisms may uncover a novel therapeutic strategy for ESRD.

show abstract

“…Some recent studies suggest NET involvement in the physiotherapy of other autoimmune diseases, such as type 1 diabetes (Schimmel et al, 2013), autoimmune vasculitisrare conditions affecting small blood vessels, particularly those of the lungs, skin and kidneys, rheumatoid arthritis (RA) (Bach et al, 2020), Felty syndrome, or psoriasis. Formation of NETS was observed in pathologies sucha s liver diseases (alcool-associated liver disease and portal hypertension), severe obesity ( D'abbondanza et al, 2019), pre-eclempsia (Moodley et al, 2020) or kidney diseases (Nakazawa et al, 2018).…”

Section: Sepsismentioning

confidence: 99%

NETs By-products and Extracellular DNA May Play a Key Role in COVID-19 Pathogenesis: Incidence on Patient Monitoring and Therapy

Thierry¹,

Roch²

2020

Preprint

View full text Add to dashboard Cite

Neutrophils play an important role as the first line of innate immune defense. One function of neutrophils, called neutrophil extracellular traps (NETs), has been discovered recently. NETs are extensive fibrous structures released extracellularly from activated neutrophils in response to infection. They are composed of cytosolic protein assembled on a scaffold of released chromatin. These structures suppress the dissemination of micro-organisms in blood by trapping them mechanically, and by exploiting coagulant function to segregate them within the circulation. In addition, NET components (DNA, histone, and granule proteins) also contribute to the triggering of an inflammatory process. NET function, however, can be regarded as a double-edged sword. On one hand, NET formation is an efficient strategy for neutralizing invading micro-organisms. On the other hand, NET can be harmful to the host, as its exposed by-products that are toxic to endothelial cells and parenchymal tissue. We present here the analogous biological and physiological features of the harmful positive amplification loop between inflammation and tissue damage induced by NETosis dysregulation and Coronavirus Disease-2019 (COVID-19) pathogenesis. Considering the rapid evolution of this disease symptoms and its lethality, we hypothesize that COVID-19 progresses under an amplifier loop, leading to an massive, uncontrolled inflammation process. We also describe the correlations of COVID-19 symptoms and biological features with those consecutive to uncontrolled NET formation causing various sterile or infectious diseases. General clinical conditions, and numerous pathological and biological features, are analogous with NETs deleterious effects. We postulate that Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) induces a disproportionate virus-induced NET release, and that this plays a key role in COVID-19 pathogenesis. While neutrophils are the principal starting point for extracellular and circulating DNA release, targeting NETs rather than neutrophils themselves may stand for an effective strategy. This paper offers an in-depth review of NET formation, function and pathogenic dysregulation, as well as of current and future therapies to control NET unbalance. As such, it enables us also to suggest new therapeutic strategies to fight COVID-19. In combination with or independent of the latest tested approaches, we propose that, in the short term, deoxyribonuclease I (DNase-1) treatment should be evaluated; we also advocate a significant increase in research on the development of toll-like receptors (TLR) and C-type Lectin like receptors (CLEC) inhibitors, and on anti-IL26 therapies.Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 15 April 2020

show abstract

Extracellular traps in kidney disease

Cited by 70 publications

References 157 publications

Neutrophil Extracellular Traps and By-Products Play a Key Role in COVID-19: Pathogenesis, Risk Factors, and Therapy

Neutrophil Extracellular Traps and By-Products Play a Key Role in COVID-19: Pathogenesis, Risk Factors, and Therapy

The Emerging Role of Innate Immunity in Chronic Kidney Diseases

NETs By-products and Extracellular DNA May Play a Key Role in COVID-19 Pathogenesis: Incidence on Patient Monitoring and Therapy

Contact Info

Product

Resources

About