La pêche miraculeuse des filets du neutrophile

Granger, Vanessa; Chaisemartin, Luc de; Chollet‐Martin, Sylvie

doi:10.1051/medsci/20143005018

Cited by 8 publications

(7 citation statements)

References 37 publications

(47 reference statements)

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“…This ability is associated with the release of neutrophil-derived enzymes. This alternative rapid mechanism would explain the role of NET formation in various acute phenomena [13].…”

Section: Stimulimentioning

confidence: 98%

“…Ex vivo, NETs are abundantly found in the intervening space of the placentas, and may contribute to the hypoxic lesions characterizing this pathology. In gout, it has been shown that sodium urate crystals are capable of inducing the formation of NET, and that these are protected from degradation by the fixation of C-reactive protein (CRP) molecules and of the complement [13]. NETs could therefore persist long enough at the joint to contribute to the establishment of chronic inflammation.…”

Section: Inflammatory Diseasesmentioning

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

135

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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.

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“…This ability is associated with the release of neutrophil-derived enzymes. This alternative rapid mechanism would explain the role of NET formation in various acute phenomena [13].…”

Section: Stimulimentioning

confidence: 98%

Section: Inflammatory Diseasesmentioning

confidence: 99%

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

Thierry

Roch

2020

JCM

135

View full text Add to dashboard Cite

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“…This process is asociated by the release of neutrophil-derived enzymes. This alternative rapid mechanism would explain the role of NETosis in certain acute phenomena (Granger et al, 2014).…”

Section: Stimulimentioning

confidence: 99%

“…Ex vivo, NETs are abundantly found in the intervening space of the placentas, and may contribute to the hypoxic lesions characterizing this pathology. In gout, it has been shown that sodium urate crystals are capable of inducing the formation of NET, and that these are protected from degradation by the fixation of C-reactive protein (CRP) molecules and of the complement (Granger et al, 2014). NETs could therefore persist long enough at the joint to contribute to the establishment of chronic inflammation.…”

Section: Inflammatory Diseasementioning

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

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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

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“…Les neutrophiles peuvent tuer les microorganismes par une multitude de mécanismes tels que la phagocytose, la libération d'enzymes qu'ils présentent au niveau de leurs granules cytoplasmiques (myéloperoxidase [MPO], élastase, protéinase-3, cathépsine G, etc. ), ou de dérivés réactifs de l'oxygène (produits par la NADPH [nicotinamide adénine dinucléotide phosphate réduit] oxydase et la MPO), ou la formation de NET (neutrophil extracellular traps) 1 [1][2][3] (➜). Certains produits libérés lors de l'activation des neutrophiles, et qui sont impliqués dans les défenses antimi- Les souris neutropéniques La plupart des modèles de souris neutropéniques ont été créés en utilisant une approche génétique visant à bloquer l'expression ou l'activité de la protéine Gfi-1 (growth factor independent-1), un répresseur de transcription qui favorise la différenciation des cellules souches hématopoïétiques en précurseurs de neutrophiles [19].…”

Section: Les Neutrophiles : Cellules Clé De L'immunité Innéeunclassified

Un nouveau modèle de souris pour comprendre le rôle des neutrophiles

Gillis

Reber

2018

Med Sci (Paris)

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Neutrophils play a key role in host defense against pathogens. They can contribute to pathological inflammation, and are thought to exacerbate tissue injury upon exposure to bacterial products, such as endotoxin (LPS). Recent findings suggest that neutrophils can also participate in adaptive immune responses and contribute to inflammation resolution. Many discoveries regarding the in vivo role of neutrophils were made possible by the use of genetically modified neutrophil-deficient mice, or by the use of neutrophil-depleting antibodies. Here we describe a new mouse model, PMN mice, in which neutrophils can be selectively depleted upon injection of diphtheria toxin. Using this model, we have recently demonstrated that neutrophils play a protective role during lethal endotoxin-induced systemic shock. This new mouse model presents several major advantages over more classical models of neutropenia, which are discussed herein.

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La pêche miraculeuse des filets du neutrophile

Cited by 8 publications

References 37 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

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

Un nouveau modèle de souris pour comprendre le rôle des neutrophiles

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