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.

scholarly journals The Emerging Role of Neutrophil Extracellular Traps in Arterial, Venous and Cancer-Associated Thrombosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yilu Zhou ◽  
Weimin Tao ◽  
Fuyi Shen ◽  
Weijia Du ◽  
Zhendong Xu ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Neutrophil Extracellular Traps ◽  
Vital Role ◽  
Extracellular Traps ◽  
Protein Components ◽  
Cancer Associated Thrombosis ◽  
Coagulation Pathway

Neutrophils play a vital role in the formation of arterial, venous and cancer-related thrombosis. Recent studies have shown that in a process known as NETosis, neutrophils release proteins and enzymes complexed to DNA fibers, collectively called neutrophil extracellular traps (NETs). Although NETs were originally described as a way for the host to capture and kill bacteria, current knowledge indicates that NETs also play an important role in thrombosis. According to recent studies, the destruction of vascular microenvironmental homeostasis and excessive NET formation lead to pathological thrombosis. In vitro experiments have found that NETs provide skeletal support for platelets, red blood cells and procoagulant molecules to promote thrombosis. The protein components contained in NETs activate the endogenous coagulation pathway to promote thrombosis. Therefore, NETs play an important role in the formation of arterial thrombosis, venous thrombosis and cancer-related thrombosis. This review will systematically summarize and explain the study of NETs in thrombosis in animal models and in vivo experiments to provide new targets for thrombosis prevention and treatment.

scholarly journals SOCE-inhibitor reduced human sperm-induced formation of neutrophil extracellular traps

Reproduction ◽  
2021 ◽  
Vol 161 (1) ◽  
pp. 21-29
Author(s):  
Fabiola Zambrano ◽  
Liliana Silva ◽  
Pamela Uribe ◽  
Ulrich Gärtner ◽  
Anja Taubert ◽  
...  
Keyword(s):  
Binding Capacity ◽  
Human Sperm ◽  
Neutrophil Extracellular Traps ◽  
Positive Control ◽  
Polymorphonuclear Neutrophils ◽  
Extracellular Dna ◽  
Dna Integrity ◽  
Extracellular Traps

Human spermatozoa activate neutrophil extracellular traps (NETs) in vitro. NETosis is an efficient mechanism through which polymorphonuclear neutrophils (PMN) capture sperm in vitro. The objective of this study was to establish the role of store-operated Ca+2 entry (SOCE) in human sperm-triggered NETs and its impact on sperm integrity and oocyte binding capacity. PMN isolated from donors were exposed to spermatozoa isolated from normozoospermic donors using the swim-up technique and were divided into the following groups: (1) sperm, (2) PMN, (3) PMN + sperm, (4) PMN (pretreated with 2-APB, SOCE inhibitor) + sperm, (5) (PMN + DNase) + sperm, and (6) (PMN + PMA) + sperm (positive control). NETs were quantified using PicoGreen® and visualised by scanning electron microscopy and immunofluorescence of extracellular DNA and neutrophil elastase. Plasma membrane, acrosome, and DNA integrity were analysed by flow cytometry, and oocyte binding was evaluated using the hemizona pellucida assay. Sperm-triggered NETosis negatively affected the sperm membrane and acrosome integrity and decreased the oocyte binding capacity. These effects were negated by an SOCE inhibitor, thus improving sperm function and achieving high oocyte binding capacity. The SOCE inhibitor significantly reduced NET formation compared with that in control PMN/sperm (P < 0.05). Collectively, these results advance the knowledge about the role of PMN in reproduction and will allow the development of strategies to block NET formation in situations of reduced fertilisation success.

scholarly journals SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology

2020 ◽  
Vol 217 (12) ◽  
Author(s):  
Flavio Protasio Veras ◽  
Marjorie Cornejo Pontelli ◽  
Camila Meirelles Silva ◽  
Juliana E. Toller-Kawahisa ◽  
Mikhael de Lima ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Tracheal Aspirate ◽  
Neutrophil Extracellular Traps ◽  
Angiotensin Converting Enzyme 2 ◽  
Extracellular Traps ◽  
Lung Epithelial ◽  
Activated Neutrophils ◽  
Epithelial Cell Death

Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2–activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19.

scholarly journals Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kotaro Matsumoto ◽  
Hidekata Yasuoka ◽  
Keiko Yoshimoto ◽  
Katsuya Suzuki ◽  
Tsutomu Takeuchi
Keyword(s):  
Flow Cytometric Analysis ◽  
Neutrophil Extracellular Traps ◽  
Platelet Factor ◽  
Extracellular Traps ◽  
Flow Cytometric ◽  
Anca Associated Vasculitis ◽  
Tlr Agonist ◽  
Tlr9 Signaling

AbstractNeutrophils form neutrophil extracellular traps (NETs), which are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Recent reports suggest that platelets stimulated via toll-like receptor (TLR) pathways can induce NETs formation. However, the mechanism underlying the involvement of platelets in NETs formation in AAV is unknown. We investigated the role of platelets in the pathogenesis of AAV. Platelets from AAV patients and healthy controls (HCs) were co-cultured with peripheral neutrophils, and NETs formation was visualized and quantified. The expression levels of TLRs on platelets were examined by flow cytometry. Platelets were treated with a TLR agonist, platelet-derived humoral factor, CXCL4 (platelet factor 4: PF4), and/or anti-CXCL4 antibody to investigate the effects of TLR–CXCL4 signaling on NETs formation. Platelets from AAV significantly upregulated NETs formation in vitro. Flow cytometric analysis revealed that the proportion of TLR9 positive platelets was significantly higher in AAV than HCs. CXCL4 released from TLR9 agonist-stimulated platelets was significantly enhanced in AAV, which subsequently increased NETs formation. Further, neutralizing anti-CXCL4 antibody significantly inhibited NETs formation enhanced by platelets from AAV. TLR9 signaling and CXCL4 release underlie the key role that platelets play in NETs formation in the pathogenesis of AAV.

scholarly journals Tissue Factor-Enriched Neutrophil Extracellular Traps Promote Immunothrombosis and Disease Progression in Sepsis-Induced Lung Injury

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao Zhang ◽  
Yilu Zhou ◽  
Mengdi Qu ◽  
Ying Yu ◽  
Zhaoyuan Chen ◽  
...  
Keyword(s):  
Lung Injury ◽  
Disease Progression ◽  
Tissue Factor ◽  
Neutrophil Extracellular Traps ◽  
Thrombin Inhibitors ◽  
Extracellular Traps ◽  
Activated Platelets ◽  
Human Blood Samples

BackgroundPatients with sepsis may progress to acute respiratory distress syndrome (ARDS). Evidence of neutrophil extracellular traps (NETs) in sepsis-induced lung injury has been reported. However, the role of circulating NETs in the progression and thrombotic tendency of sepsis-induced lung injury remains elusive. The aim of this study was to investigate the role of tissue factor-enriched NETs in the progression and immunothrombosis of sepsis-induced lung injury.MethodsHuman blood samples and an animal model of sepsis-induced lung injury were used to detect and evaluate NET formation in ARDS patients. Immunofluorescence imaging, ELISA, Western blotting, and qPCR were performed to evaluate in vitro NET formation and tissue factor (TF) delivery ability. DNase, an anti-TF antibody, and thrombin inhibitors were applied to evaluate the contribution of thrombin to TF-enriched NET formation and the contribution of TF-enriched NETs to immunothrombosis in ARDS patients.ResultsSignificantly increased levels of TF-enriched NETs were observed in ARDS patients and mice. Blockade of NETs in ARDS mice alleviated disease progression, indicating a reduced lung wet/dry ratio and PaO2 level. In vitro data demonstrated that thrombin-activated platelets were responsible for increased NET formation and related TF exposure and subsequent immunothrombosis in ARDS patients.ConclusionThe interaction of thrombin-activated platelets with PMNs in ARDS patients results in local NET formation and delivery of active TF. The notion that NETs represent a mechanism by which PMNs release thrombogenic signals during thrombosis may offer novel therapeutic targets.

scholarly journals Role of neutrophil extracellular traps in radiation resistance of invasive bladder cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Surashri Shinde-Jadhav ◽  
Jose Joao Mansure ◽  
Roni F. Rayes ◽  
Gautier Marcq ◽  
Mina Ayoub ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neutrophil Extracellular Traps ◽  
Polymorphonuclear Neutrophils ◽  
Dependent Manner ◽  
Potential Therapeutic Target ◽  
Extracellular Traps ◽  
Tumor Immune Microenvironment

AbstractRadiation therapy (RT) is used in the management of several cancers; however, tumor radioresistance remains a challenge. Polymorphonuclear neutrophils (PMNs) are recruited to the tumor immune microenvironment (TIME) post-RT and can facilitate tumor progression by forming neutrophil extracellular traps (NETs). Here, we demonstrate a role for NETs as players in tumor radioresistance. Using a syngeneic bladder cancer model, increased NET deposition is observed in the TIME of mice treated with RT and inhibition of NETs improves overall radiation response. In vitro, the protein HMGB1 promotes NET formation through a TLR4-dependent manner and in vivo, inhibition of both HMGB1 and NETs significantly delays tumor growth. Finally, NETs are observed in bladder tumors of patients who did not respond to RT and had persistent disease post-RT, wherein a high tumoral PMN-to-CD8 ratio is associated with worse overall survival. Together, these findings identify NETs as a potential therapeutic target to increase radiation efficacy.

scholarly journals Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Y. Shi ◽  
J. S. Gauer ◽  
S. R. Baker ◽  
H. Philippou ◽  
S. D. Connell ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Structure Formation ◽  
In Vitro Study ◽  
Neutrophil Extracellular Traps ◽  
Vitro Study ◽  
Extracellular Traps ◽  
Clot Structure

AbstractNeutrophils and neutrophil extracellular traps (NETs) have been shown to be involved in coagulation. However, the interactions between neutrophils or NETs and fibrin(ogen) in clots, and the mechanisms behind these interactions are not yet fully understood. In this in vitro study, the role of neutrophils or NETs on clot structure, formation and dissolution was studied with a combination of confocal microscopy, turbidity and permeation experiments. Factor (F)XII, FXI and FVII-deficient plasmas were used to investigate which factors may be involved in the procoagulant effects. We found both neutrophils and NETs promote clotting in plasma without the addition of other coagulation triggers, but not in purified fibrinogen, indicating that other factors mediate the interaction. The procoagulant effects of neutrophils and NETs were also observed in FXII- and FVII-deficient plasma. In FXI-deficient plasma, only the procoagulant effects of NETs were observed, but not of neutrophils. NETs increased the density of clots, particularly in the vicinity of the NETs, while neutrophils-induced clots were less stable and more porous. In conclusion, NETs accelerate clotting and contribute to the formation of a denser, more lysis resistant clot architecture. Neutrophils, or their released mediators, may induce clotting in a different manner to NETs, mediated by FXI.

scholarly journals Neutrophil Extracellular Traps Facilitate Sympathoexcitation After Traumatic Brain Injury Via HMGB1/AP1 Signaling Pathway

2021 ◽  
Author(s):  
Kaixin Zhu ◽  
Xiaoxiang Hou ◽  
Xiaolin Qu ◽  
Wen Chen ◽  
Kun Chen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Diffuse Axonal Injury ◽  
Neutrophil Extracellular Traps ◽  
Control Group ◽  
Extracellular Traps ◽  
Important Form

Abstract Background: Traumatic brain injury (TBI) usually accompanies with sympathetic excitation, and paradoxical sympathetic hyperactivity (PSH) may be detrimental to the prognosis of TBI sufferers. Neutrophils can form neutrophil extracellular traps (NETs) to get involved in the neuroinflammation after TBI. As an important form of NETs, HMGB1 were found to activate the expression of AP1, which can increase the formation of IL-1β in microglia. Considering that IL-1β is able to regulate sympathoexcitation, it is reasonable to infer that HMGB1/AP1 signaling plays an important role in sympathoexcitation after TBI. Methods: In this present study, rat model with diffuse axonal injury (DAI) was established. The existance of NETs and the expression level of HMGB1/AP1/IL-1β in the paraventricular nucleus (PVN) after DAI were examined by immunofluorescence and Western blot (WB). The role of HMGB1/AP1 in the activation of microglia, secretion of IL-1β and sympathoexcitaiton were identified in vitro. Moreover, stereotaxic injection of anti-HMGB1 or HMGB1 was conducted to further validate the effect of HMGB1/AP1 pathway on sympathoexcitation after TBI.Results: The indicators of sympathoexcitation, including mean arterial pressure and serum catecholamine, increased and peaked at 72 hours after TBI. The formation of NETs was observed in PVN after injury, whereas, no NETs were found in the control group. And meanwhile, levels of NETs in PVN were higher than that in the para-PVN tissues after the injury. In vitro experiments showed that HMGB1 can promote the activation of microglia as well as increase the expression of AP1 and IL-1β. In vivo experiments suggested HMGB1 have an impact on the expression of AP1 and IL-1β in the PVN, and further controlling the sympathoexcitation after TBI.Conclusion: NETs might mediate sympathoexcitation after TBI through microglial activation in the PVN in a HMGB1/AP1/IL-1β dependent way.

scholarly journals THE ROLE OF PLATELETS IN FORMATION OF NEUTROPHIL EXTRACELLULAR TRAPS IN PATIENTS WITH IMMUNOCOMPLEX PATHOLOGY

2016 ◽  
pp. 66-70
Author(s):  
J. V. Zubkova ◽  
I. A. Novikova ◽  
V. V. Zhelezko
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Rheumatoid Factor ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
In Vitro Cultures ◽  
Systemic Lupus ◽  
Extracellular Traps

The article presents the results of the assessment of the role of platelets in formation of extracellular traps by neutrophils. We have detected the ability of platelets to oppress the formation of extracellular traps by neutrophils in vitro cultures in patients with rheumatoid arthritis (RA) (n = 42) and systemic lupus erythematosus (SLE) (n = 24), but not in patients with hemorrhagic vasculitis (GW) (n = 15). The study has revealed the interrelation of NETosis and rheumatoid factor in patients with RA and SLE, as well as NET formation and number of platelets in patients with GW.

scholarly journals The Impact of Various Reactive Oxygen Species on the Formation of Neutrophil Extracellular Traps

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Tina Kirchner ◽  
Sonja Möller ◽  
Matthias Klinger ◽  
Werner Solbach ◽  
Tamás Laskay ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Reactive Oxygen ◽  
Neutrophil Extracellular Traps ◽  
Oxygen Species ◽  
Extracellular Traps ◽  
Comprehensive Manner ◽  
The Impact ◽  
Net Release

The formation of neutrophil extracellular traps (NETs) depends on the generation of reactive oxygen species (ROS). Previous studies revealed that both NADPH oxidase and myeloperoxidase (MPO) are required for NET release. However, the contribution of various ROS as well as the role of mitochondria-derived ROS has not been addressed so far. In the present study we aimed to investigate in a systematic and comprehensive manner the contribution of various ROS and ROS-generating pathways to the PMA-induced NET release. By using specific inhibitors, the role of both NADPH oxidase- and mitochondria-derived ROS as well as the contribution of superoxide dismutase (SOD) and MPO on the NET release was assessed. We could demonstrate that NADPH oxidase function is crucial for the formation of NETs. In addition, we could clearly show the involvement of MPO-derived ROS in NET release. Our results, however, did not provide evidence for the role of SOD- or mitochondria-derived ROS in NET formation.

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