ArticleBritish journal of anaesthesia2022
Reduction of NETosis by targeting CXCR1/2 reduces thrombosis, lung injury, and mortality in experimental human and murine sepsis.
Article in British journal of anaesthesia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Neutrophil extracellular traps (NETs) and NETosis in alcohol-associated diseases: A systematic review.Alcohol, clinical & experimental research · 2025Pooled it
- Bilirubin reduces mortality in sepsis models by inhibiting NOX2-mediated formation of neutrophil extracellular traps.Redox report : communications in free radical research · 2026Article
- NETosis in the Kidney, Liver, and Lung of Mice With Cecal Ligation and Puncture-Induced Sepsis and the Ameliorating Effects of Adipose-Derived Stem Cell Exosomes.The Kaohsiung journal of medical sciences · 2026Article
- Neutrophil extracellular traps in thrombosis of hematologic malignancies: Underlying mechanisms and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- FOLR3+neutrophils contribute to sepsis by exacerbating hyper-inflammation.Genes and immunity · 2026Article
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- Multicellular crosstalk in neutrophilic asthma: unraveling the pathogenic web of steroid resistance and emerging precision therapies.Journal of translational medicine · 2026Review
- Roles of neutrophil extracellular traps in cancer immunotherapy resistance and therapeutic targeting.Biomarker research · 2026Review
- Caffeine inhibited the hyperoxia-induced A2AR-ERK/p38 MAPK-IL-8 pathway in type II alveolar epithelial cells to suppress NETs formation in bronchopulmonary dysplasia.Pediatric research · 2026Article
- WWC1 deficiency exacerbates sepsis-induced lung injury by promoting NETosis, M1 and M2b macrophage recruitment, and pyroptosis via YAP1 and STING pathways.Journal of inflammation (London, England) · 2026Article
- ERG-deficient endothelium identifies IL-8/CXCR2 axis as a therapeutic target for resolving neutrophilic lung vascular injury.JCI insight · 2026Article
- PP4 modulates macrophage-neutrophil crosstalk to restrict CCL5 -driven NETosis in sepsis.Redox biology · 2026Article
- Dysregulation of Neutrophil-Endothelial Communication in Sepsis: Mechanisms and Therapeutic Perspectives.Cells · 2026Review
- Neutrophil Extracellular Traps in Cancer Metastasis: From Mechanistic Understanding to Targeted Therapy.Current oncology (Toronto, Ont.) · 2026Review
- Roles of anesthetics in modulating neutrophil extracellular traps formation: a review of current literature.Annals of medicine and surgery (2012) · 2026Article
- Multimodal characterization of flow-induced thrombus initiation and growth in extracorporeal membrane oxygenation.Scientific reports · 2026Article
- Non-apoptotic Regulated Cell Death Mechanisms in Sepsis and their Therapeutic Potential.Inflammation · 2026Review
- Peritoneal neutrophil extracellular traps contribute to septic AKI via peritoneal IL-17A and distant organ CXCL-1/ CXCL-2 pathway in abdominal sepsis.Scientific reports · 2026Article
- Anticoagulants beyond coagulation: repurposing heparin to mitigate immunothrombosis and inflammatory cascades in sepsis.Frontiers in pharmacology · 2026Review
- Interleukins in community-acquired pneumonia: from biomarkers to precision medicine.Frontiers in immunology · 2026Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundNeutrophil extracellular traps (NETs) facilitate bacterial clearance but also promote thrombosis and organ injury in sepsis. We quantified ex vivo NET induction in septic humans and murine models of sepsis to identify signalling pathways that may be modulated to improve outcome in human sepsis.
methodsNET formation in human donor neutrophils was quantified after incubation with plasma obtained from patients with sepsis or systemic inflammation (double-blinded assessment of extracellular DNA using immunofluorescence microscopy). NET formation (% neutrophils forming NETs) was correlated with plasma cytokine levels (MultiPlex assay). Experimental sepsis (caecal ligation and puncture or intraperitoneal injection of Escherichia coli) was assessed in C57/BL6 male mice. The effect of pharmacological inhibition of CXCR1/2 signalling (reparixin) on NET formation, organ injury (hepatic, renal, and cardiac biomarkers), and survival in septic mice was examined.
resultsNET formation was higher after incubation with plasma from septic patients (median NETs=25% [10.5-46.5%]), compared with plasma obtained from patients with systemic inflammation (14% [4.0-23.3%]; P=0.02). Similar results were observed after incubation of plasma from mice with neutrophils from septic non-septic mice. Circulating CXCR1/2 ligands correlated with NETosis in patients (interleukin-8; r=0.643) and mice (macrophage inflammatory protein-2; r=0.902). In experimental sepsis, NETs were primarily observed in the lungs, correlating with fibrin deposition (r=0.702) and lung injury (r=0.692). Inhibition of CXCR1/2 using reparixin in septic mice reduced NET formation, multi-organ injury, and mortality, without impairing bacterial clearance.
conclusionCXCR1/2 signalling-induced NET formation is a therapeutic target in sepsis, which may be guided by ex vivo NET assays.
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Registered trials
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