Neutrophil extracellular traps in homeostasis and disease

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 20, 2024

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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Circulating neutrophil extracellular trap remnants as a biomarker to predict outcomes in lupus nephritis

Lupus Science & Medicine, Journal Year: 2024, Volume and Issue: 11(1), P. e001038 - e001038

Published: Jan. 1, 2024

Objective To determine if the serum levels of neutrophil extracellular trap (NET) remnants (Elastase-DNA and HMGB1-DNA complexes) at time a lupus nephritis (LN) flare predict renal outcomes in following 24 months. Methods This was retrospective study performed prospectively followed cohorts. The included two cohorts: an exploratory cohort to assess association between NET remnant presence active LN, separate LN utility over subsequent Results Ninety-two individuals were (49 systemic erythematosus (SLE), 23 inactive SLE 20 healthy controls (HC)). significantly higher patients with compared HC (p<0.0001 for both those (36%) had without (Elastase-DNA: p=0.03; HMGB1-DNA: p=0.02). 109 patients. Patients proliferative than non-proliferative p<0.0001; p=0.0003). baseline odds not achieving complete remission OR 2.34, p=0.007; 2.61, p=0.009) progressing severe impairment 2.84, p=0.006; 2.04, p=0.02) months after flare. Conclusions Elastase-DNA complexes outcomes, suggesting they could be used identify requiring more aggressive therapy onset.

Language: Английский

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Expression of molecular markers and synergistic anticancer effects of chemotherapy with antimicrobial peptides on glioblastoma cells

Cancer Chemotherapy and Pharmacology, Journal Year: 2024, Volume and Issue: 93(5), P. 455 - 469

Published: Jan. 27, 2024

Language: Английский

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Biomaterials for immunomodulation in wound healing

Regenerative Biomaterials, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 1, 2024

Abstract The substantial economic impact of non-healing wounds, scarring, and burns stemming from skin injuries is evident, resulting in a financial burden on both patients the healthcare system. This review paper provides an overview skin’s vital role guarding against various environmental challenges as body’s largest protective organ associated developments biomaterials for wound healing. We first introduce composition tissue intricate processes healing, with special attention to crucial immunomodulation acute chronic wounds. highlights how imbalance immune response, particularly wounds underlying health conditions such diabetes immunosuppression, hinders normal healing stages. Then, this distinguishes between traditional wound-healing strategies that create optimal microenvironment recent peptide-based modulate cellular responses facilitate closure. Additionally, we highlight importance considering stages process. By integrating advanced materials engineering in-depth understanding biology, approach holds promise reshaping field management ultimately offering improved outcomes

Language: Английский

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Inflammation‐, immunothrombosis,‐ and autoimmune‐feedback loops may lead to persistent neutrophil self‐stimulation in long COVID

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(8)

Published: Aug. 1, 2024

Understanding the pathophysiology of long COVID is one most intriguing challenges confronting contemporary medicine. Despite observations recently made in relevant molecular, cellular, and physiological domains, it still difficult to say whether post-acute sequelae COVID-19 directly correspond consequences severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This work hypothesizes that neutrophils neutrophil extracellular traps (NETs) production are at interconnection three positive feedback loops which initiated phase SARS-CoV-2 infection, involve inflammation, immunothrombosis, autoimmunity. phenomenon could be favored by fact may bind penetrate neutrophils. The ensuing strong stimulation leads a progressive amplification an exacerbated uncontrolled NETs production, potentially persisting for months beyond continuous self-stimulation leads, turn, systemic micro-thromboses, autoantibodies, whose significant include persistence endothelial multiorgan damage, vascular complications.

Language: Английский

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Alterations in neutrophil mRNA profiles in multiple sclerosis and identification of candidate genes for further investigation

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 17, 2025

Introduction Multiple sclerosis (MS) is a chronic and debilitating inflammatory disease of the central nervous system (CNS), characterized by demyelination neurodegeneration. Emerging evidence implicates neutrophils in MS pathogenesis, particularly through processes like neutrophil extracellular traps (NETs) formation degranulation, which may exacerbate inflammation autoimmunity. Methods RNA sequencing peripheral blood from patients healthy controls identified differentially expressed genes (DEGs). Pathway enrichment protein–protein interaction (PPI) analyses highlighted potential biomarkers, validated using reverse transcription quantitative PCR (RT-qPCR) enzyme-linked immunosorbent assay (ELISA). Results Our analysis 1,968 DEGs patients, comprising 1,068 upregulated 900 downregulated genes. revealed significant involvement immune processes, including antigen presentation, B T cell receptor signaling, intracellular signaling cascades, degranulation. Notably, KEGG pivotal role for formation, process increasingly associated with PPI network pinpointed five key hub genes— LCN2 , LTF ELANE CAMP CTSG —as players neutrophil-mediated modulation. Protein-level validation ELISA confirmed elevated levels consistent transcriptomic findings, further supporting their as biomarkers. Subsequent RT-qPCR demonstrated robust diagnostic these genes, area under curve (AUC) values 0.952 (LCN2), 0.827 (LTF), 0.968 (ELANE), 0.950 (CAMP), 0.862 (CTSG). Discussion These findings uncover previously underappreciated driven alterations gene expression linked to modulation NET formation. The LCN2, demonstrate strong potential, offering new avenue non-invasive diagnostics. Beyond clinical utility, this study highlights importance neutrophil-driven responses MS, providing mechanistic insights into complex interplay between innate adaptive immunity demyelinating diseases. Furthermore, suggest that targeting neutrophil-specific such NETs could mitigate damage provide novel therapeutic approaches treatment. results lay groundwork future studies exploring strategies functions MS.

Language: Английский

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The Role of Crosstalk between Nets and Keratinocytes in Skin Immunity

Journal of Investigative Dermatology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Neutrophilic inflammation in bronchiectasis

European Respiratory Review, Journal Year: 2025, Volume and Issue: 34(176), P. 240179 - 240179

Published: April 1, 2025

Noncystic fibrosis bronchiectasis, hereafter referred to as is a chronic, progressive lung disease that can affect people of all ages. Patients with clinically significant bronchiectasis have chronic cough and sputum production, well recurrent respiratory infections, fatigue impaired health-related quality life. The pathophysiology has been described vicious vortex inflammation, recurring airway infection, mucociliary clearance damage promotes the development progression disease. This review describes pivotal role neutrophil-driven inflammation in pathogenesis bronchiectasis. Delayed neutrophil apoptosis increased necrosis enhance dysregulated failure resolve this contributes sustained inflammation. excessive release serine proteases, such elastase, cathepsin G proteinase 3, protease–antiprotease imbalance correlates progression. While there are currently no licensed therapies treat will explore evolving evidence for neutrophilic novel treatment target meaningful clinical benefits.

Language: Английский

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Between good and evil: Complexation of the human cathelicidin LL-37 with nucleic acids

Biophysical Journal, Journal Year: 2023, Volume and Issue: 123(11), P. 1316 - 1328

Published: Nov. 2, 2023

The innate immune system provides a crucial first line of defense against invading pathogens attacking the body. As only member human cathelicidin family, antimicrobial peptide LL-37 has been shown to have antiviral, antifungal, and antibacterial properties. In complexation with nucleic acids, is suggested maintain its beneficial health effects while also acting as condensation agent for acid. Complexes formed by acids be immunostimulatory positive impact on system. However, some studies suggest that in circumstances, LL-37/nucleic acid complexes may contributing factor autoimmune disorders such psoriasis systemic lupus erythematosus. This review comprehensive discussion research highlighting complexes, well discussing observed detrimental effects. We will emphasize why it important investigate elucidate structural characteristics, patterns within complexation, their mechanisms action, shed light intricate physiological seemingly contradictory role response.

Language: Английский

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