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Peroxynitrite-mediated oxidation of albumin to the protein-thiyl free radical.

Nitric oxide reacts with superoxide to produce peroxynitrite, which may be an important mediator of oxidant-induced cellular injury. Here we report that peroxynitrite is able to oxidize a protein, bovine serum albumin (BSA), to the corresponding protein-thiyl free radical as demonstrated by electron paramagnetic resonance (EPR)-spin-trapping experiments with both alpha-phenyl-N-tert-butyl nitrone (PBN) and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). BSA radical adduct yields increased with pH indicating peroxynitrite anion as its main forming agent. Reaction with peroxynitrite may be another aspe

Homotrimeric MMP-9 is an active hitchhiker on alpha-2-macroglobulin partially escaping protease inhibition and internalization through LRP-1.

Proteolysis is a crucial process in life, tightly controlled by numerous natural protease inhibitors. In human blood, alpha-2-macroglobulin is an emergency protease inhibitor preventing coagulation and damage to endothelia and leukocytes. With the use of a unique protease trapping mechanism, alpha-2-macroglobulin lures active proteases into its snap-trap, shields these from potential substrates and 'flags' their complex for elimination by receptor-mediated endocytosis. Matrix metalloprotease-9/gelatinase B is a secreted protease increased in blood of patients with inflammations, vascular disor

Gonococcal Defenses against Antimicrobial Activities of Neutrophils.

Neisseria gonorrhoeae initiates a strong local immune response that is characterized by copious recruitment of neutrophils to the site of infection. Neutrophils neutralize microbes by mechanisms that include phagocytosis, extracellular trap formation, production of reactive oxygen species, and the delivery of antimicrobial granular contents. However, neutrophils do not clear infection with N. gonorrhoeae. N. gonorrhoeae not only expresses factors that defend against neutrophil bactericidal components, but it also manipulates neutrophil production and release of these components. In this review

Temporal transcriptomic profiling of pulmonary thromboembolism reveals persistent NETosis- and ferroptosis-associated gene signatures and enhanced thrombolysis with adjunctive DNase I.

OBJECTIVE: To investigate the dynamic pathophysiology of pulmonary thromboembolism (PTE), focusing on the roles of neutrophil extracellular traps (NETs) and ferroptosis, and to evaluate intravenous DNase I as an adjunct to recombinant tissue plasminogen activator (rt-PA). METHODS: A rabbit autologous thrombus PTE model was established using 62 animals for the time-course and therapeutic-intervention experiments. Disease progression was assessed at days 1, 3, 7, and 14 using histology (collagen volume fraction, CVF), serology (e.g., MPO-DNA, PAI-1, t-PA), and RNA-sequencing. Bioinformatics ide…

Liver-Targeted Gallium-Polyphenol Network by Disrupting the ROS/NETs/PANoptosis Axis for Precision Acute Liver Injury Therapy.

Acute liver injury (ALI), driven by diverse insults such as drug toxicity and ischemia-reperfusion, poses a high mortality risk and lacks targeted therapies. While reactive oxygen species (ROS), neutrophil extracellular traps (NETs), and a coordinated cell death pathway PANoptosis have been implicated, their interplay as a unified pathogenic axis remains elusive. Here, by integrating multi-omics analyses of clinical databases and patient samples, we systematically identified and validated the ROS/NETs/PANoptosis axis as a central driver of hepatocyte damage across multiple ALI etiologies. To t…

Itaconate Modulates Neutrophil Homeostasis to Ameliorate Airway Inflammation in Diesel Exhaust Particles-exacerbated Asthma via Inhibiting NETs Formation.

Particulate matter exposure, especially diesel exhaust particles (DEP), can exacerbate neutrophilic airway inflammation which presents corti … , neutrophil-derived ITA helped maintain immune homeostasis by reducing the formation of neutrophil extracellular traps (NETs), which further inhibited Th17 cell differentiation in DEP-exacerbated asthma. Our results delineate the dual immunoregulatory function of neutrophils in DEP-induced corticosteroid-resistant asthma, wherein they simultaneously propagate inflam …

Spectral Flow Cytometry Method for Immunophenotyping Neutrophil Activation and NETs in an Acute Dust Exposure Model.

BACKGROUND: Although the contributions of neutrophils and neutrophil extracellular trap (NET) in chronic respiratory diseases associated with environmental dust inhalation has advanced, changes in neutrophil populations and their response following acute dust inhalation are relatively limited. Our understanding of neutrophil response during acute lung injury relies on blood and lung samples, which limit investigations on neutrophil dynamics such as neutrophil production, release, trafficking, and NET formation in response to acute exposures. METHODS: To address this limitation, we designed a

Intraperitoneal translocation of gut microbiota induces NETosis and promotes endometriosis.

BACKGROUND: Endometriosis is a debilitating gynaecological disorder with an elusive pathogenesis. While gut microbiota dysbiosis has been implicated, the causal role of gut-peritoneum microbial translocation and the specific mechanisms driving disease progression remain elusive. Notably, the role of peritoneal neutrophils and neutrophil extracellular traps (NETs) in the development of endometriosis remains unknown. OBJECTIVE: This study aims to delineate the pathogenic pathway linking gut microbiota to peritoneal neutrophil activation and the development of endometriosis. DESIGN: We combined…

Tricyclazole alleviates Fonsecaea pedrosoi-induced immune suppression of neutrophils by inhibiting DHN-melanin biosynthesis.

INTRODUCTION: Chromoblastomycosis (CBM) is a chronic cutaneous infection caused by dematiaceous fungi, characterized by therapeutic challeng … and fungal antioxidant enzymes, as well as reactive oxygen species (ROS) production and neutrophil extracellular traps (NETs) formation in human neutrophils. The in vivo mouse model was used to evaluate inflammatory responses, neutrophil-related markers, and fungal clearance. RESULTS: In vitro tests showed TCZ dose-dependently inhibited fungal DHN-melanin synthesis …

DNase1 reverses peribronchial inflammation in murine explants incubated with activated neutrophils.

INTRODUCTION: Neutrophil extracellular traps (NETs) are chromatin-based structures released by activated neutrophils that are associated with microvascular thrombosis and pulmonary inflammation. These are adverse effects that are relevant in ECMO-associated lung injury. Although enzymatic NET degradation by DNase1 represents a potential anti-inflammatory strategy, its anti-inflammatory effects in the lung tissue and on vascular endothelial growth factor (VEGF) signalling have received limited investigation. We used a tissue-architecture-preserving murine lung explant model to characterise infl…

Transfusion-related acute lung injury: experimental models to study pathogenesis and therapeutic strategies.

Transfusion-related acute lung injury (TRALI) is a life-threatening complication of blood transfusion, with mortality rates exceeding 40% in critically ill patients. Despite its clinical severity, TRALI pathogenesis remains unclear, leaving clinicians struggling to fully understand and manage it due to its unpredictable onset, complex causes, and lack of available treatments. Recent advances in experimental models, including in vitro, ex vivo, and in vivo models, have revealed novel mechanisms such as neutrophil extracellular trap formation, gut-microbiota crosstalk, and endothelial and neutro

Peripheral immune profiling highlights a dynamic role of low-density granulocytes in myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune neuromuscular disease marked by dysregulation of several immune cell populations. Here w … but induce a pro-inflammatory Th1/Th17 response. They also display enhanced spontaneous neutrophil extracellular traps (NETs) formation and basal reactive oxygen species (ROS) production. LDGs decreased after intravenous immunoglobulin and increased after prolonged immunotherapy in minimal manifestation status (MM), with reduced pro-inflammatory activity. Bulk RNA s …

Association of NETs Markers with Clinical and Radiological Outcomes in Patients with Acute Ischemic Stroke Undergoing Thrombectomy: Does Heparin Treatment Modify This?

The aim of this study is to investigate the association of neutrophil extracellular traps (NETs) markers with clinical and radiological outcomes in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) and assess the effect of periprocedural heparin during EVT on NETs markers and their association with outcomes. From 198 AIS patients included in the MRCLEAN-MED trial, randomized to receive EVT with (N = 104) or without (N = 94) low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h, n = 104), blood samples were collected at baseline, 1 h, and 24 h…

[Temporal Expression of NETosis Marker CitH3 in Deep Vein Thrombosis in Mice].

OBJECTIVES: To detect the expression changes of citrullinated histone H3 (CitH3) during the development of deep vein thrombosis (DVT) in mice, and to explore its value in estimating the time to thrombosis. METHODS: The inferior vena cava (IVC) of mice was ligated to establish a thrombosis model induced by congestion. Mice were sacrificed under excessive anesthesia at 0 h, 1 d, 3 d, 5 d, 7 d, 10 d, 14 d and 21 d after the modeling, respectively. The congested IVC segments (0 h after modeling) and the thrombosed IVC segments (1-21 days after modeling) were extracted. Immunohistochemistry and do

Neutrophils in Toxocara canis infection: Effector functions, immune evasion and crosstalk with type 2 immunity.

Toxocara canis is an important zoonotic parasite with significant clinical relevance to both veterinary and human health. While neutrophils … their several effector mechanisms, including degranulation, reactive oxygen species, and neutrophil extracellular traps, in vitro studies demonstrate that neutrophils are unable to kill Toxocara canis larvae, highlighting the parasite's sophisticated immune evasion strategies. However, in vivo, neutrophils exhibit striking plasticity. They adopt an N2 phenotype via t …

Внеклеточная ДНК и Deoxiribonuc Alternation Activity как потенциальные биомаркеры воспаления в множестве склерозов.

Нейроинфламмация играет важнейшую роль в патофизиологии множественных склерозов (MS), включая сложные взаимодействия между реактивными видами кислорода (ROS), цитокинами, хемокинами и иммунными клетками. Среди них нейтрофилы способствуют устойчивому воспалению путем обезвоживания, производства ROS и высвобождения нейтрофильных внеклеточных ловушек (NETs). Внеклеточная ДНК (ecDNA), являющаяся ключевым компонентом сетей, может выступать в качестве автоантигена, стимулирующего хроническое воспаление и повреждение тканей. Кроме того, нарушение НЕТ и деградация ecDNA в результате деоксирибонуковой

Совпадение в аннотации оригинала
Neuroinflammation plays a critical role in the pathophysiology of multiple sclerosis (MS), involving complex interactions between reactive oxygen species (ROS), cytokines, chemokines, and immune cells. Among these, neutrophils contribute to sustained inflammation through degranulation, ROS production, and the release of neutrophil extracellular traps (NETs).…

Neutrophil glucose flux as a therapeutic target in antiphospholipid syndrome.

Neutrophil hyperactivity and neutrophil extracellular trap release (NETosis) appear to play important roles in the pathogenesis of the thromboinflammatory autoimmune disease known as antiphospholipid syndrome (APS). The understanding of neutrophil metabolism has advanced tremendously in the past decade, and accumulating evidence suggests that a variety of metabolic pathways guide neutrophil activities in health and disease. Our previous work characterizing the transcriptome of APS neutrophils revealed that genes related to glycolysis, glycogenolysis, and the pentose phosphate pathway (PPP) wer

Colchicine Alleviates Rosacea by Inhibiting Neutrophil Inflammation Activated by the TLR2 Pathway.

Rosacea is a chronic facial inflammatory skin disease that occurs with dysfunction of the immune system. Colchicine was reported to have anti-inflammatory properties. However, the impact of colchicine on rosacea remains unclear. In the present study, the phenotype of rosacea lesions was evaluated by the redness score, inflammatory biomarkers were analyzed by reverse transcription PCR (RT‒PCR), and the infiltration of inflammatory cells was assessed by IHC analysis and immunofluorescence in a rosacea-like mouse model. In vitro, RT‒PCR was used to identify the inflammatory factors that Toll-like

NET burden in left atrial blood is associated with biomarkers of thrombosis and cardiac injury in patients with enlarged left atria.

BACKGROUND: Emerging data suggest an association between left atrial (LA) enlargement, thrombus formation, and ischemic stroke. However, it is unknown what may mediate such clot formation in LA dysfunction. Neutrophils promote large vessel occlusion and microthrombosis via neutrophil extracellular trap (NET) release, thus lying at the interface of inflammation, thrombosis, and fibrosis. APPROACH: We conducted a prospective all-comers cohort study in patients undergoing catheterization procedures with atrial transseptal access (MitraClip, MC; left atrial appendage closure, LAAC; pulmonary vein

Galectin-3 Mediates NETosis and Acts as an Autoantigen in Systemic Lupus Erythematosus-Associated Diffuse Alveolar Haemorrhage.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with enhanced NETosis and impaired degradation of neutrophil extracellular traps (NETs). Galectin-3 is a β-galactoside binding protein and is associated with neutrophil functions as well as involved in mediating autoimmune disorders. In this study, we plan to examine the associations of galectin-3 with the pathogenesis of SLE and NETosis. Galectin-3 expression levels were determined in peripheral blood mononuclear cells (PBMCs) of SLE patients for the association with lupus nephritis (LN) or correlation of SLE disease activity…