A metabolic perspective of the neutrophil life cycle: new avenues in immunometabolism

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Neutrophils are the most abundant innate immune cells. Multiple mechanisms allow them to engage a wide range of metabolic pathways for biosynthesis and bioenergetics mediating biological processes such as development in bone marrow antimicrobial activity ROS production NET formation, inflammation tissue repair. We first discuss recent work on neutrophil functions regulate granulopoiesis, migration trafficking well effector functions. then syndromes with impaired that influenced by genetic environmental factors nutrient availability usage. Here, we particularly focus role specific macronutrients, glucose, fatty acids, protein, micronutrients vitamin B3, regulating biology how this regulation impacts host health. A special section review primarily discusses ways deficiencies could impact increase infection susceptibility. emphasize biochemical approaches explore metabolism relation Lastly, opportunities challenges neutrophil-centered therapeutic immune-driven diseases highlight unanswered questions guide future discoveries.

Language: Английский

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How Do ROS Induce NETosis? Oxidative DNA Damage, DNA Repair, and Chromatin Decondensation

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1307 - 1307

Published: Oct. 16, 2024

Neutrophil extracellular traps (NETs) are intricate, DNA-based, web-like structures adorned with cytotoxic proteins. They play a crucial role in antimicrobial defense but also implicated autoimmune diseases and tissue injury. The process of NET formation, known as NETosis, is regulated cell death mechanism that involves the release these unique to neutrophils. NETosis heavily dependent on production reactive oxygen species (ROS), which can be generated either through NADPH oxidase (NOX) or mitochondrial pathways, leading NOX-dependent NOX-independent respectively. Recent research has revealed an intricate interplay between ROS production, DNA repair, formation different contexts. UV radiation trigger combined apoptosis, apoNETosis, driven by repair. Similarly, calcium ionophore-induced both repair key components, only partial role. In case bacterial infections, early stages pivotal. Interestingly, serum-free conditions, spontaneous occurs NOX-derived ROS, early-stage inhibition halting process, while late-stage increases it. balance processes appears critical factor regulating pathways being activated depending nature stimulus. These findings not deepen our understanding mechanisms behind suggest potential therapeutic targets for conditions where NETs contribute disease pathology.

Language: Английский

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N-benzyl-N-methyldecane-1-amine derived from garlic ameliorates UVB-induced photoaging in HaCaT cells and SKH-1 hairless mice

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 26, 2025

Skin tissue is susceptible to oxidative stress-induced senescence provoked by ultraviolet (UV) exposure in our daily lives, resulting photoaging. Herein, we explore whether N-benzyl-N-methyldecan-1-amine (BMDA) derived from garlic ameliorates UVB-induced To address this issue, HaCaT keratinocytes were exposed UVB irradiation under BMDA treatment. The presence of substantially reduced ROS levels a dose-dependent manner. administration counteracted the β-galactosidase assay. Treatment with also rescued UVB-exposed cells (S phase; 18.3 25.8%) cell cycle arrest, similar level observed untreated normal cells. These findings might support observation that elevated γ-H2AX, DNA damage marker, following administration. Additionally, treatment indirectly melanin synthesis melanocytes since failed inhibit tyrosinase activity, crucial enzyme synthesis. topical application on skin SKH-1 hairless mice diminished wrinkle formation, supported recovered collagen and thickness epidermis dermis, compared those UVB-control mice. Finally, expression inflammatory cytokine transcripts such as TNF-α, IL-1β, IL-4, IL-6 tissues. This finding further Immunofluorescence microscopy, which showed decrease IL-1β during Altogether, mitigates photoaging reducing production, protecting against damage, suppressing it has been proposed an effective anti-photoaging molecule.

Language: Английский

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Targeting neutrophils extracellular traps, a promising anti-thrombotic therapy for natural products from traditional Chinese herbal medicine

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117310 - 117310

Published: Sept. 2, 2024

Thrombi are the main cause of vascular occlusion and contribute significantly to cardiovascular events death. Neutrophils extracellular traps (NETs)-induced thrombosis plays a vital role in thrombotic complications it takes responsibility for resistance fibrinolysis. However, conventional anti-thrombotic therapies inadequate treat NETs-induced but carry high risk bleeding. Consequently, increased attention has shifted towards exploring novel treatments targeting NETs. Interestingly, accumulating evidences prove that natural products from traditional Chinese herbal medicines have great potential mitigate through inhibiting generous NETs formation degrading excessive In this review, we elaborated degradation highlighted its pivotal immunothrombosis interactions with platelets coagulation factors. Since available drugs deficient, further summarized compounds which exert effective actions on regulating also effects. Our findings underscore diverse effects NETs, including relieving inflammation oxidative stress neutrophils, neutrophils activation DNA efflux, suppressing granule proteins release, reducing histones promoting degradation. This review aims highlight significance lay groundwork developing agents medicines.

Language: Английский

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Cyclic stretch enhances neutrophil extracellular trap formation

BMC Biology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 18, 2024

Neutrophils, the most abundant leukocytes circulating in blood, contribute to host defense and play a significant role chronic inflammatory disorders. They can release their DNA form of extracellular traps (NETs), which serve as scaffolds for capturing bacteria various blood cells. However, uncontrolled formation NETs (NETosis) lead excessive activation coagulation pathways thrombosis. Once neutrophils are migrated infected or injured tissues, they become exposed mechanical forces from surrounding environment. impact transient changes tissue mechanics due natural process aging, infection, injury, cancer on remains unknown. To address this gap, we explored interactive effects substrate stiffness cyclic stretch NETosis. Primary were cultured silicon-based with levels 30 300 kPa at least 3 h under static conditions 5% 10%, mirroring biomechanics aged young arteries.

Language: Английский

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Mitochondrial Transplantation/Transfer: Promising Therapeutic Strategies for Spinal Cord Injury

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 52, P. 441 - 450

Published: May 1, 2025

Language: Английский

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Neutrophil PPIF exacerbates lung ischemia–reperfusion injury after lung transplantation by promoting calcium overload-induced neutrophil extracellular traps formation

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113051 - 113051

Published: Sept. 4, 2024

Language: Английский

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Human HLA prolongs the host inflammatory response in Streptococcus suis serotype 2 infection compared to mouse H2 molecules

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Nov. 14, 2023

Streptococcus suis ( S. ) is widely acknowledged as a significant zoonotic pathogen in Southeast Asia and China, which has led to substantial number of fatalities both swine humans. Despite the prevalent use mice primary animal model study pathogenesis, differences major histocompatibility complex (MHC) between humans underscore ongoing exploration for more suitable effective model. In this study, humanized transgenic HLA-A11/DR1 genotypes were used evaluate HLA murine H2 infection. Following intravenous administration suspensions, we investigated bacterial load, cytokine profiles, pathological alterations, immune cell recruitment Wild-type (WT) across different post-infection time points. Relative WT mice, exhibited heightened pro-inflammatory cytokines, exacerbated tissue damage, increased granulocyte with impaired resolution, notably pronounced during late infection stage. Additionally, our examination clearance rates suggests that primarily influences mitochondrial reactive oxygen species (ROS) production, affects killing capacity macrophages stage The reduced IL-10 production lower levels regulatory T cells could underlie their compromised resolution ability. Intervention promotes inflammatory regression stages mice. Our findings sensitivity infection, effectively mirroring response seen serve an optimal investigating pathogenic therapeutic mechanisms associated sepsis other infectious diseases.

Language: Английский

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Ischemia–reperfusion injury after spinal cord decompressive surgery—An in vivo rat model

Animal Models and Experimental Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 3, 2024

Abstract Background Although decompression surgery is the optimal treatment for patients with severe degenerative cervical myelopathy (DCM), some individuals experience no improvement or even a decline in neurological function after surgery, spinal cord ischemia–reperfusion injury (SCII) identified as primary cause. Spinal compression results local ischemia and blood perfusion following fundamental to SCII. However, owing inadequate perioperative flow monitoring, direct evidence regarding occurrence of SCII lacking. The objective this study was establish suitable animal model investigating underlying mechanism (DCM) elucidate alterations within before decompression. Methods Twenty‐four Sprague–Dawley rats were allocated three groups: DCM group (cervical group, implanted material canal, n = 8), DCM‐D removal from canal 4 weeks implantation, SHAM (sham operation, 8). Von Frey test, forepaw grip strength, gait assessed post‐implantation. evaluated using magnetic resonance imaging. Local monitored during sacrificed 1 week observe morphological changes compressed decompressed segments cord. Additionally, NeuN expression oxidative damage marker 8‐oxoG DNA analyzed. Results Following compression, abnormal mechanical pain worsened, decrease strength observed 1–4 weeks. Upon decompression, subsided, restored; however, neither reached level sham operation group. Decompression leads an increase flow, indicating improved number NeuN‐positive cells exceeded that but remained lower than Notably, higher observed, suggesting stress Conclusion This deemed analyzing decompressive laminectomy, we posit obtained are comparable clinical progression post‐decompression exhibit analogous alterations. revealed ischemic reperfusion concomitant damage, which plausibly underlies deterioration

Language: Английский

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