ArticleCritical care (London, England)2019
Neutrophil extracellular traps (NETs) exacerbate severity of infant sepsis.
Article in Critical care (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm.Biomaterials · 2021Trial
- Dexmedetomidine attenuates sepsis-associated NET formation and Th17 polarization through α2-adrenergic receptor-associated regulation of hepatic HPD.Archives of pharmacal research · 2026Article
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- Immune research progress of Slit2-Robo signaling axis in chronic obstructive pulmonary disease: a narrative review.Journal of thoracic disease · 2026Review
- Delayed disulfiram targeting GSDMD-NETs axis rescues sepsis by limiting bacterial spread and lung injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Systems biology approaches to unravelling neonatal sepsis and potential for precision diagnostics and therapeutics.Frontiers in pharmacology · 2026Review
- Platelet activation plays a pro-inflammatory role in myasthenia gravis.Nature communications · 2025Article
- Shared immune biomarkers in necrotizing enterocolitis and neonatal sepsis identified via bioinformatics and machine learning.Scientific reports · 2025Article
- Live fast, die young: neutrophils streamline their metabolism to maximize inflammation.Infection and immunity · 2025Review
- NETosis and pyroptosis of immune cells in sepsis.Journal of translational internal medicine · 2025Article
- LPS promotes the production of ROS in neutrophils to regulate their killing activity against Mycobacterium tuberculosis.Scientific reports · 2025Article
- Mechanism of hydroxychloroquine in the treatment of obstetric antiphospholipid syndrome by inhibiting NETs-induced trophoblast pyroptosis.Molecular biology reports · 2025Article
- MMP9Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neutrophil Extracellular Traps Promote AIM2-Dependent Microglial Pyroptosis Following Stroke.Aging and disease · 2025Article
- Mechanisms and immune crosstalk of neutrophil extracellular traps in response to infection.mBio · 2025Review
- Neutrophil extracellular traps-related genes contribute to sepsis-associated acute kidney injury.BMC nephrology · 2025Article
- Immunomodulation in Pediatric Sepsis: A Narrative Review.Journal of clinical medicine · 2025Review
- Mitochondria sense bacterial lactate and drive release of neutrophil extracellular traps.Cell host & microbe · 2025Article
- Complement-mediated and direct activation of human neutrophils induced byFrontiers in immunology · 2025Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundNeutrophil extracellular traps (NETs) are innate defense mechanisms that are also implicated in the pathogenesis of organ dysfunction. However, the role of NETs in pediatric sepsis is unknown.
methodsInfant (2 weeks old) and adult (6 weeks old) mice were submitted to sepsis by intraperitoneal (i.p.) injection of bacteria suspension or lipopolysaccharide (LPS). Neutrophil infiltration, bacteremia, organ injury, and concentrations of cytokine, NETs, and DNase in the plasma were measured. Production of reactive oxygen and nitrogen species and release of NETs by neutrophils were also evaluated. To investigate the functional role of NETs, mice undergoing sepsis were treated with antibiotic plus rhDNase and the survival, organ injury, and levels of inflammatory markers and NETs were determined. Blood samples from pediatric and adult sepsis patients were collected and the concentrations of NETs measured.
resultsInfant C57BL/6 mice subjected to sepsis or LPS-induced endotoxemia produced significantly higher levels of NETs than the adult mice. Moreover, compared to that of the adult mice, this outcome was accompanied by increased organ injury and production of inflammatory cytokines. The increased NETs were associated with elevated expression of Padi4 and histone H3 citrullination in the neutrophils. Furthermore, treatment of infant septic mice with rhDNase or a PAD-4 inhibitor markedly attenuated sepsis. Importantly, pediatric septic patients had high levels of NETs, and the severity of pediatric sepsis was positively correlated with the level of NETs.
conclusionThis study reveals a hitherto unrecognized mechanism of pediatric sepsis susceptibility and suggests that NETs represents a potential target to improve clinical outcomes of sepsis.
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