scholarly journals Neutrophil Extracellular Traps and Microcrystals

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Balázs Rada
Keyword(s):  
Early Stage ◽  
Neutrophil Extracellular Traps ◽  
Calcium Pyrophosphate ◽  
Cholesterol Crystals ◽  
Extracellular Traps ◽  
Calcium Pyrophosphate Dehydrate ◽  
Innate Immune Mechanism ◽  
Silica Crystals ◽  
Net Release ◽  
Urate Crystals

Neutrophil extracellular traps represent a fascinating mechanism by which PMNs entrap extracellular microbes. The primary purpose of this innate immune mechanism is thought to localize the infection at an early stage. Interestingly, the ability of different microcrystals to induce NET formation has been recently described. Microcrystals are insoluble crystals with a size of 1–100 micrometers that have different composition and shape. Microcrystals have it in common that they irritate phagocytes including PMNs and typically trigger an inflammatory response. This review is the first to summarize observations with regard to PMN activation and NET release induced by microcrystals. Gout-causing monosodium urate crystals, pseudogout-causing calcium pyrophosphate dehydrate crystals, cholesterol crystals associated with atherosclerosis, silicosis-causing silica crystals, and adjuvant alum crystals are discussed.

scholarly journals The state of art of neutrophil extracellular traps in protozoan and helminthic infections

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
César Díaz-Godínez ◽  
Julio C. Carrero
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Parasitic Infections ◽  
Parasitic Diseases ◽  
Helminth Parasites ◽  
Extracellular Traps ◽  
Helminthic Infections ◽  
Bacteria And Fungi ◽  
Net Release

AbstractNeutrophil extracellular traps (NETs) are DNA fibers associated with histones, enzymes from neutrophil granules and anti-microbial peptides. NETs are released in a process denominated NETosis, which involves sequential steps that culminate with the DNA extrusion. NETosis has been described as a new mechanism of innate immunity related to defense against different pathogens. The initial studies of NETs were carried out with bacteria and fungi, but currently a large variety of microorganisms capable of inducing NETs have been described including protozoan and helminth parasites. Nevertheless, we have little knowledge about how NETosis process is carried out in response to the parasites, and about its implication in the resolution of this kind of disease. In the best case, the NETs entrap and kill parasites in vitro, but in others, immobilize the parasites without affecting their viability. Moreover, insufficient studies on the NETs in animal models of infections that would help to define their role, and the association of NETs with chronic inflammatory pathologies such as those occurring in several parasitic infections have left open the possibility of NETs contributing to pathology instead of protection. In this review, we focus on the reported mechanisms that lead to NET release by protozoan and helminth parasites and the evidence that support the role of NETosis in the resolution or pathogenesis of parasitic diseases.

NETosis: how vital is it?

Blood ◽  
2013 ◽  
Vol 122 (16) ◽  
pp. 2784-2794 ◽  
Author(s):  
Bryan G. Yipp ◽  
Paul Kubes
Keyword(s):  
Innate Immunity ◽  
Cell Death ◽  
Critical Role ◽  
Neutrophil Extracellular Traps ◽  
Live Cell ◽  
Extracellular Traps ◽  
Cell Death Pathway ◽  
A Cell ◽  
Net Release

Abstract In this review, we examine the evidence that neutrophil extracellular traps (NETs) play a critical role in innate immunity. We summarize how NETs are formed in response to various stimuli and provide evidence that NETosis is not universally a cell death pathway. Here we describe at least 2 different mechanisms by which NETs are formed, including a suicide lytic NETosis and a live cell or vital NETosis. We also evaluate the evidence for NETs in catching and killing pathogens. Finally, we examine how infections are related to the development of autoimmune and vasculitic diseases through unintended but detrimental bystander damage resulting from NET release.

scholarly journals Neutrophil extracellular traps and thrombosis in COVID-19

2020 ◽  
Author(s):  
Yu Zuo ◽  
Melanie Zuo ◽  
Srilakshmi Yalavarthi ◽  
Kelsey Gockman ◽  
Jacqueline A. Madison ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Histone H3 ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Extracellular Trap ◽  
Dna Complexes ◽  
Extracellular Traps ◽  
Free Dna ◽  
Extracellular Trap ◽  
Net Release ◽  
D Dimer

ABSTRACTHere, we report on four patients whose hospitalizations for COVID-19 were complicated by venous thromboembolism (VTE). All demonstrated high levels of D-dimer as well as high neutrophil-to-lymphocyte ratios. For three patients, we were able to test sera for neutrophil extracellular trap (NET) remnants and found significantly elevated levels of cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3. Neutrophil-derived S100A8/A9 (calprotectin) was also elevated. Given strong links between hyperactive neutrophils, NET release, and thrombosis in many inflammatory diseases, the potential relationship between NETs and VTE should be further investigated in COVID-19.

scholarly journals Therapeutic Targeting of Neutrophil Extracellular Traps in Atherogenic Inflammation

2019 ◽  
Vol 119 (04) ◽  
pp. 542-552 ◽  
Author(s):  
Kristof Van Avondt ◽  
Lars Maegdefessel ◽  
Oliver Soehnlein
Keyword(s):  
Disease Risk ◽  
Neutrophil Extracellular Traps ◽  
Dnase I ◽  
Inflammasome Activation ◽  
Extracellular Traps ◽  
Thrombotic Complications ◽  
Atherothrombotic Disease ◽  
Coronary Events ◽  
Reactive Oxidants ◽  
Net Release

AbstractNeutrophils and neutrophil extracellular traps (NETs) have a robust relationship with atherothrombotic disease risk, which led to the idea that interfering with the release of NETs therapeutically would ameliorate atherosclerosis. In human studies, acute coronary events and the pro-thrombotic state cause markedly elevated levels of circulating deoxyribonucleic acid (DNA) and chromatin, suggesting that DNase I might produce cardiovascular benefit. DNase I reproduced the phenotype of peptidylarginine deiminase 4 (PAD4) deficiency and showed a significant benefit for atherothrombotic disease in experimental mouse models. However, the mechanisms of benefit remain unclear. Insights into the mechanisms underlying NET release and atherogenic inflammation have come from transgenic mouse studies. In particular, the importance of neutrophil NET formation in promoting atherothrombotic disease has been shown and linked to profound pro-inflammatory and pro-thrombotic effects, complement activation and endothelial dysfunction. Recent studies have shown that myeloid deficiency of PAD4 leads to diminished NET formation, which in turn protects against atherosclerosis burden, propagation of its thrombotic complications and notably macrophage inflammation in plaques. In addition, oxidative stress and neutrophil cholesterol accumulation have emerged as important factors driving NET release, likely involving mitochondrial reactive oxidants and neutrophil inflammasome activation. Further elucidation of the mechanisms linking hyperlipidaemia to the release of NETs may lead to the development of new therapeutics specifically targeting atherogenic inflammation, with likely benefit for cardiovascular diseases.

Gasdermin D inhibition prevents multiple organ dysfunction during sepsis by blocking NET formation

Blood ◽  
2021 ◽  
Author(s):  
Camila Meirelles Silva ◽  
Carlos W. S. Wanderley ◽  
Flavio P Veras ◽  
Fabiane Sonego ◽  
Daniele Carvalho Nascimento ◽  
...  
Keyword(s):  
Organ Dysfunction ◽  
Neutrophil Extracellular Traps ◽  
Multiple Organ ◽  
Organ Injury ◽  
Multiple Organ Dysfunction ◽  
Extracellular Traps ◽  
Highly Correlated ◽  
Net Release ◽  
Worse Prognosis ◽  
Novel Therapeutic

Multiple organ dysfunction is the most severe outcome of sepsis progression and is highly correlated with a worse prognosis. Excessive neutrophil extracellular traps (NETs) are critical players in the development of organ failure during sepsis. Therefore, interventions targeting NET release would likely effectively prevent NET-based organ injury associated with this disease. Herein, we demonstrate that the pore-forming protein gasdermin D (GSDMD) is active in neutrophils from septic humans and mice and plays a crucial role in NET release. Inhibition of GSDMD with disulfiram or genic deletion abrogated NET formation, reducing multiple organ dysfunction and sepsis lethality. Mechanistically, we demonstrate that during sepsis, activation of the caspase-11/GSDMD pathway controls NET release by neutrophils during sepsis. In summary, our findings uncover a novel therapeutic use for disulfiram and suggest that GSDMD is a therapeutic target to improve sepsis treatment.

scholarly journals Neutrophil Extracellular Traps Generation Relates with Early Stage and Vascular Complications in Systemic Sclerosis

2020 ◽  
Vol 9 (7) ◽  
pp. 2136 ◽  
Author(s):  
Kevin Didier ◽  
Delphine Giusti ◽  
Sebastien Le Jan ◽  
Christine Terryn ◽  
Celine Muller ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Early Stage ◽  
Systemic Disease ◽  
Vascular Complications ◽  
Neutrophil Extracellular Traps ◽  
Digital Ulcers ◽  
Serum Factors ◽  
Net Production ◽  
Extracellular Traps ◽  
Enhanced Production

Systemic sclerosis (SSc) is a systemic disease characterized by a great clinical and immunological heterogeneity whose pathophysiology is still being unraveled. Recently, innate immunity has been proposed to participate to the pathogenesis of SSc. In this study, we investigated the release of neutrophil extracellular traps (NETs) according to patient phenotype. Polymorphonuclear neutrophils (PMN) from 34 SSc patients and 26 healthy controls were stimulated by serum from SSc or healthy subject. NETs were visualized using epifluorescence microscope after DNA, myeloperoxidase, and Histone H3 tagging. Area of NETs were quantified using an original macro running in ImageJ® software. PMN from SSc patients were significantly more prone to releasing NETs than control PMN after autologous stimulation. PMN from patients with severe vascular complications (pulmonary arterial hypertension, digital ulcers) produced more NETs than PMN from other SSc patients and their aberrant NET production appeared to be sustained over time. In patients with pulmonary interstitial disease or extensive cutaneous fibrosis, NET production was high at an early stage of the disease before progressively decreasing. Both serum factors and PMN activation status were involved in the enhanced production of NETs in SSc. Consequently, neutrophils and especially NETosis represent new physiopathological and therapeutic fields in SSc.

scholarly journals Nanoparticles Equipped with α2,8-Linked Sialic Acid Chains Inhibit the Release of Neutrophil Extracellular Traps

Nanomaterials ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 610 ◽  
Author(s):  
Bornhöfft ◽  
Viergutz ◽  
Kühnle ◽  
Galuska
Keyword(s):  
Reactive Oxygen Species ◽  
Cystic Fibrosis ◽  
Sialic Acid ◽  
Neutrophil Extracellular Traps ◽  
Oxygen Species ◽  
Inhibitory Effects ◽  
Myristate Acetate ◽  
Extracellular Traps ◽  
Free Sialic Acid ◽  
Net Release

Neutrophils can combat the invasion of pathogens by the formation of neutrophil extracellular traps (NETs). The NET mechanism is not only an effective tool for combating pathogens, but is also associated with diseases. Therefore, NETs are a potential target for combating pathologies, such as cystic fibrosis and thrombosis. We investigated the potential of nanoparticles, which were modified with α2,8-linked sialic acid chains, to modulate NET release during phorbol myristate acetate stimulation. Interestingly, when these nanoparticles were applied, the formation of reactive oxygen species was partly inhibited and the release of NET was counteracted. However, although the release of NET fibers was prevented, the nuclei still lost their characteristic segmented structure and became swollen, indicating that only the release, and not complete activation was suppressed. Intriguingly, coincubation of α2,8-sialylated particles with free sialic acid chains prevented the outlined inhibitory effects. Thus, the sialic acid chains must be attached to a linker molecule to generate an active bioconjugate that is able to inhibit the release of NET.

scholarly journals The total terpenoids of Celastrus orbiculatus (TTC) inhibit NOX-dependent formation of PMA-induced neutrophil extracellular traps (NETs)

2018 ◽  
Vol 16 ◽  
pp. 205873921880566
Author(s):  
Li Tao ◽  
Min Xu ◽  
Yanqing Liu
Keyword(s):  
Enzymatic Activity ◽  
Early Stage ◽  
Neutrophil Extracellular Traps ◽  
Human Neutrophils ◽  
Ros Generation ◽  
Ros Production ◽  
Celastrus Orbiculatus ◽  
Traditional Chinese Herbal Medicine ◽  
Extracellular Traps ◽  
Anti Inflammatory

Previously, we identified that Celastrus orbiculatus, a traditional Chinese herbal medicine, exhibited prominent anti-inflammatory and anti-tumor activities. More recently, the formation of neutrophil extracellular traps (NETs) or NETosis has been recognized as a critical pathological event in the development of inflammatory and autoimmune diseases. The present study is aimed to explore the pharmacological effect of the total terpenoids from the stems of C. orbiculatus (TTC) on NETosis and underlying mechanisms, which may provide fundamental knowledge for future utilization of the Chinese medicine. Human neutrophils were isolated by density gradient centrifugation; lactase dehydrogenase (LDH) assay was used to detect cytotoxic effect of TTC on neutrophils. Moreover, we established phorbol-12-myristate-13-acetate (PMA)-induced NETosis. Quantitative and qualitative study of PMA-induced NET release was labeled by SYTOX™ Green. ROS production was determined by flow cytometry. The neutrophil NADPH oxidase (NOX) activity was assessed by lucigenin chemiluminescence assay, and the phosphorylation of NOX subunit was analyzed by immunoblot assay. TTC (5–80 μg.mL−1) had no predominant neutrophil cytotoxicity after 4 h exposure. PMA (200 ng.mL−1) significantly induced the formation of NETs after 4 h stimulus, whereas TTC dose-dependently (5–80 μg.mL−1) inhibited the process. TTC (40 μg.mL−1) blocked neutrophil elastase (NE) and myeloperoxidase (MPO) translocation from cytoplasm to nucleus and disrupted the formation of NET-associated deoxyribonucleic acid (DNA)–MPO and DNA–NE complexes. Moreover, TTC dose-dependently blocked PMA-mediated ROS production, and inhibited the NOX enzymatic activity of neutrophils upon PMA stimulus for 1 h. Finally, TTC suppressed PMA-induced phosphorylation of NOX subunit p40phox on Thr154 residue. TTC inhibited PMA-induced NOX phosphorylation, thereby suppressing NOX enzymatic activity and ROS generation in neutrophils undergoing NETosis. Consequently, TTC disrupted NETosis in the early stage of NOX-dependent NETs formation, which might serve as a promising anti-inflammatory agent by targeting suicidal NETosis.

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