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Neutrophil Extracellular Traps Block Fibrinolysis in Ischemic Stroke.

OBJECTIVES: Intravenous thrombolysis (IVT) failure in acute ischemic stroke (AIS) is frequent, but its causes remain elusive. We investigated whether biologically relevant intrathrombus concentrations of tissue plasminogen activator (tPA) were achieved in failed IVT and whether neutrophil extracellular traps (NETs) contributed to this therapeutic failure. METHODS: In this monocenter cohort study, 205 thrombi from AIS patients were analyzed. A total of 83 of these thrombi were compared for tPA content and 53 for their susceptibility to ex vivo thrombolysis according to IVT status. An additiona…

Neutrophil Extracellular Traps in Patients with Intracerebral Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is a subtype of stroke frequently resulting in severe disability. Secondary mechanisms after ICH include neuroinflammation and development of perihematomal edema. Neutrophil extracellular traps (NETs) mediate infection defense and are involved in disease processes affecting the nervous system, including immunothrombosis and blood-brain barrier disruption. We aimed to assess NETs in ICH and their potential contribution to outcome measures. METHODS: We conducted a prospective, single-center cohort study recruiting patients with ICH within 2…

Нейтрофильные внеклеточные ловушки по заболеваниям центральной нервной системы.

Нейтрофильные внеклеточные ловушки (NETs) представляют собой комплексы, содержащие фибрил ДНК и антимикробные пептиды, которые высвобождаются нейтрофилами в ответ на патогенную стимуляцию. На момент их обнаружения нейтрофильная внеклеточная ловушка содержала активные вещества, такие как нейтрофильная эластаза (NE) и миэлопероксидаза (MPO). Хотя изначально считалось, что ННЕТ являются средством для врожденной иммунной системы в борьбе с микробными вторжениями, в настоящее время было отмечено, что они оказывают более широкое воздействие на организм. В ходе недавних исследований ННЕТ были связаны

Совпадение в аннотации оригинала
Neutrophil Extracellular Traps (NETs) are complexes containing DNA fibrils and antimicrobial peptides that are released by neutrophils in response to pathogen stimulation. At the time of their discovery, the neutrophil extracellular trap contained active substances such as Neutrophil Elastase (NE) and myeloperoxidase (MPO). Although NETs were initially thoug…

Neutrophil Extracellular Traps (NETs) in health and disease.

Neutrophil extracellular traps (NETs) are web-like structures composed of DNA, histones, and antimicrobial proteins that extend the defensive repertoire of neutrophils beyond classical phagocytosis and degranulation. Initially considered solely antimicrobial, NETs are now recognized as dynamic regulators of immunity, inflammation, and tissue remodeling. Their formation is orchestrated by the generation of reactive oxygen species, neutrophil elastase-mediated chromatin remodeling, and peptidyl arginine deiminase 4-driven histone citrullination. At the same time, clearance involves DNase activit…

Giardia duodenalis triggered neutrophil extracellular traps in goats.

Giardia duodenalis is a globally distributed zoonotic parasite primarily transmitted through the fecal-oral route, infecting various vertebrates, and the infection of which is prevalent in goats. Immune cells play a crucial role in pathogens invasion, and neutrophil extracellular traps (NETs) released by neutrophils serve as a non-specific defense mechanism against pathogens including parasites. In this study, we investigated the characteristics, components, and molecular mechanisms of goat NETs upon stimulation with G. duodenalis trophozoites. This study demonstrates that G. duodenalis trigge…

Neutrophil extracellular traps promote tumor chemoresistance to anthracyclines.

The microenvironment plays an important role in promoting tumor cell chemoresistance, but the mechanisms responsible for this effect are not clear. Here, using models of multiple myeloma (MM) and solid cancers, we demonstrate a novel mechanism mediated by neutrophils, a major cell population in the bone marrow (BM), that protects cancer cells from chemotherapeutics. We show that in response to tumor-derived soluble factors, BM neutrophils release their DNA in the form of neutrophil extracellular traps (NETs). Cell-free DNA derived from NETs is then taken up by tumor cells via endocytosis and l…

Neutrophil Extracellular Traps (NET) and SARS-CoV-2.

NETosis is a type of neutrophil extinction that outcome in the liberation of extracellular chromatin and protein accumulation, which contains antiviral proteins, produced by an external pathogen. Neutrophils can show bipolar action in special circumstances. This event, along with other circumstances, involves COVID-19. Neutrophil extracellular traps (NETs) are involved in the pathogenesis of COVID-19 by creating a pro-inflammatory and pre-coagulation state that leads to numerous organ losses. This form of host defense, which is promoted by neutrophils, is closely related to the known cytokine …

Neutrophil extracellular traps regulate ischemic stroke brain injury.

Ischemic stroke prompts a strong inflammatory response, which is associated with exacerbated outcomes. In this study, we investigated mechanistic regulators of neutrophil extracellular trap (NET) formation in stroke and whether they contribute to stroke outcomes. NET-forming neutrophils were found throughout brain tissue of ischemic stroke patients, and elevated plasma NET biomarkers correlated with worse stroke outcomes. Additionally, we observed increased plasma and platelet surface-expressed high-mobility group box 1 (HMGB1) in stroke patients. Mechanistically, platelets were identified as

Neutrophil Extracellular Traps in Asthma: Friends or Foes?

Asthma is a chronic inflammatory disease characterized by variable airflow limitation and airway hyperresponsiveness. A plethora of immune and structural cells are involved in asthma pathogenesis. The roles of neutrophils and their mediators in different asthma phenotypes are largely unknown. Neutrophil extracellular traps (NETs) are net-like structures composed of DNA scaffolds, histones and granular proteins released by activated neutrophils. NETs were originally described as a process to entrap and kill a variety of microorganisms. NET formation can be achieved through a cell-death process,…

Neutrophil Extracellular Traps: Signaling Properties and Disease Relevance.

Neutrophil extracellular traps (NETs) are characterized as extracellular DNA fibers comprised of histone and cytoplasmic granule proteins. NETs were first described as a form of innate response against pathogen invasion, which can capture pathogens, degrade bacterial toxic factors, and kill bacteria. Additionally, NETs also provide a scaffold for protein and cell binding. Protein binding to NETs further activate the coagulation system which participates in thrombosis. In addition, NETs also can damage the tissues due to the proteins they carry. Many studies have suggested that the excessive fo…

Neutrophil Extracellular Traps in Children With Meningococcal Sepsis.

OBJECTIVES: Children with meningococcal sepsis are highly at risk for fulminant disease, multiple organ failure, and death. Recently, neutrophil extracellular traps levels have been indicated as a marker for severity in different kinds of sepsis. Our aim was to study the role of neutrophil extracellular traposis in meninogococcal sepsis in children. DESIGN: We measured myeloperoxidase-DNA, a marker for neutrophil extracellular traps, in serum of meningococcal sepsis patients upon admission to PICU, at 24 hours, and at 1 month and studied the association with clinical outcome. Subsequently, we…

Neutrophil extracellular traps involvement in corneal fungal infection.

PURPOSE: Neutrophils release neutrophil extracellular traps (NETs) when defending against invading microorganisms. We investigated the existence of NETs in fungal keratitis. METHODS: Fourteen patients with unilateral fungal keratitis were included. Detailed information about each patient was recorded, including (1) patient history (onset of symptoms and previous therapy), (2) ocular examination findings by slit-lamp biomicroscopy, (3) laboratory findings from direct smear examination and culture of corneal scrapings, (4) NET formation, and (5) treatment strategy and prognosis. Immunofluoresce…

Neutrophil extracellular traps can activate alternative complement pathways.

The interaction between neutrophils and activation of alternative complement pathway plays a pivotal role in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). ANCAs activate primed neutrophils to release neutrophil extracellular traps (NETs), which have recently gathered increasing attention in the development of AAV. The relationship between NETs and alternative complement pathway has not been elucidated. The current study aimed to investigate the relationship between NETs and alternative complement pathway. Detection of components of alternative com…

Human neutrophils produce extracellular traps against Paracoccidioides brasiliensis.

Neutrophils play an important role as effector cells and contribute to the resistance of the host against microbial pathogens. Neutrophils are able to produce extracellular traps (NETs) in response to medically important fungi, including Aspergillus spp., Candida albicans and Cryptococcus gattii. However, NET production in response to Paracoccidioides brasiliensis has yet to be studied. We have demonstrated that human neutrophils produce NETs against both conidia and yeasts of P. brasiliensis. Although the NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) did not alter NET production …

Neutrophil extracellular traps: casting the NET over pathogenesis.

Neutrophil extracellular traps (NETs) are considered to be part of the human innate immunity because they trap and kill pathogens. NETs are formed by activated neutrophils and consist of a DNA backbone with embedded antimicrobial peptides and enzymes. They are involved in host defense during pneumococcal pneumonia, streptococcal necrotizing fasciitis, appendicitis and insemination. Recently, bacterial virulence factors that counteract NETs have been identified. These include the degradation of the NET-backbone by DNases enabling the liberation of bacteria from NETs, as well as capsule formatio…

Neutrophil extracellular traps and extracellular histones potentiate IL-17 inflammation in periodontitis.

Neutrophil infiltration is a hallmark of periodontitis, a prevalent oral inflammatory condition in which Th17-driven mucosal inflammation leads to destruction of tooth-supporting bone. Herein, we document that neutrophil extracellular traps (NETs) are early triggers of pathogenic inflammation in periodontitis. In an established animal model, we demonstrate that neutrophils infiltrate the gingival oral mucosa at early time points after disease induction and expel NETs to trigger mucosal inflammation and bone destruction in vivo. Investigating mechanisms by which NETs drive inflammatory bone los…

Endothelial Dysfunction Induced by Extracellular Neutrophil Traps Plays Important Role in the Occurrence and Treatment of Extracellular Neutrophil Traps-Related Disease.

Many articles have demonstrated that extracellular neutrophil traps (NETs) are often described as part of the antibacterial function. However, since the components of NETs are non-specific, excessive NETs usually cause inflammation and tissue damage. Endothelial dysfunction (ED) caused by NETs is the major focus of tissue damage, which is highly related to many inflammatory diseases. Therefore, this review summarizes the latest advances in the primary and secondary mechanisms between NETs and ED regarding inflammation as a mediator. Moreover, the detailed molecular mechanisms with emphasis on

Neutrophil Extracellular Traps in Atherosclerosis and Cardiovascular Disease.

Atherosclerosis is a chronic inflammatory disease of the arterial wall and the leading pathological basis of cardiovascular morbidity and mortality worldwide. Neutrophil extracellular traps (NETs), web-like chromatin structures armed with histones, myeloperoxidase, and serine proteases, have emerged as active participants in vascular inflammation and thrombosis. Under physiological conditions, NETs contribute to host defense and immunothrombosis, but excessive or persistent NET formation drives endothelial injury, plaque progression, and acute coronary events. However, how NETs shift from prot…

RAD51 stabilizes neutrophil extracellular traps to compartmentalize inflammation.

Neutrophil extracellular traps (NETs) feature a branched chromatin architecture whose origin and function remain unknown. We found that NET branching is mediated by RAD51, a protein generating DNA junctions during DNA recombination repair. Pharmacological inhibition, RAD51 knockdown, or GEN1 and RuvC resolvase treatment reduced branching and destabilized NETs, whereas RAD51 up-regulation by different stimuli generated NETs with variable stability. RAD51 inhibition during murine pulmonary Aspergillus fumigatus infection dismantled NETs and reduced lung cytokines. However, the increased accumula…

Inflammasome Activation and Neutrophil Extracellular Traps in Atherosclerosis.

The deposition of cholesterol containing cholesterol crystals and the infiltration of immune cells are features of atherosclerosis. Although … against infiltrated neutrophils, a form of cell death characterized by the formation of neutrophil extracellular traps (NETs), which, in turn, prime macrophages to enhance inflammasome-mediated inflammatory responses. Colchicine, an anti-inflammatory drug effective in cardiovascular disease, is expected to inhibit cholesterol crystal-induced NLRP3 inflammasome activ …