ArticleJCI insight2023
Platelet factor 4 limits neutrophil extracellular trap- and cell-free DNA-induced thrombogenicity and endothelial injury.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
- Insights Into the Role of Platelet Factor 4 in Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2026Review
- Research progress on neutrophil extracellular traps in sepsis‑induced coagulopathy (Review).Molecular medicine reports · 2026Review
- Single-cell Sequencing Reveals Neutrophil Extracellular Traps in Association with Endotheliopathy and Immunothrombosis in Hepatitis B Virus-related Acute-on-chronic Liver Failure.Journal of clinical and translational hepatology · 2026Article
- Mechanobiology of cancer-associated thrombosis: from molecular mechanisms to therapeutic innovation.Journal of nanobiotechnology · 2026Review
- Systemic inflammatory markers predict mortality in autoimmune thyroiditis: threshold-driven risk stratification and prognostic insights from a nationwide cohort.Hormones (Athens, Greece) · 2026Article
- Circulating Clues in Ménière's Disease: Elevated Cell-Free DNA and a Pro-Inflammatory Signature in Patients' Blood.International journal of molecular sciences · 2026Article
- Cell-Free DNA-Based Theranostics for Inflammatory Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mitochondria as Inducers of Neutrophil Extracellular Traps.Inflammation · 2026Review
- The Nodding syndrome cerebrospinal fluid proteome: a lens into neurodevelopmental failure consistent with environmentally triggeredFrontiers in molecular neuroscience · 2026Article
- Interferon receptor gene dosage differentially regulates hypoxia-induced platelet activation and pulmonary hypertension in down syndrome.Frontiers in immunology · 2026Article
- Cell-free DNA in sepsis: from molecular insights to clinical management.Military Medical Research · 2025Review
- Significance of neutrophil extracellular traps and low-density granulocytes in advanced chronic kidney disease (stage 5D) cases with COVID-19.Renal failure · 2025Article
- Emodin Alleviates Sepsis-Induced Multiorgan Damage by Inhibiting NETosis through Targeting Neutrophils BCL-10.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Beyond hemostasis, the immunomodulatory nature of platelets.Research and practice in thrombosis and haemostasis · 2025Review
- Platelet factor 4 modulates endothelial cell antimicrobial activity to enhance bacterial clearance and improve sepsis outcomes.bioRxiv : the preprint server for biology · 2025Article
- Platelets as drivers of immunothrombosis in rheumatic diseases.Nature reviews. Rheumatology · 2025Review
- Neutrophils and NETs in Pathophysiology and Treatment of Inflammatory Bowel Disease.International journal of molecular sciences · 2025Review
- Neutrophils secrete exosome-associated DNA to resolve sterile acute inflammation.Nature cell biology · 2025Article
- CELL FREE DNA-BASED PREDICTION OF PROGNOSIS FOR PATIENTS ON VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION.Shock (Augusta, Ga.) · 2025Article
- Diagnostic biomarkers and immune infiltration profiles common to COVID-19, acute myocardial infarction and acute ischaemic stroke using bioinformatics methods and machine learning.BMC neurology · 2025Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Plasma cell-free DNA (cfDNA), a marker of disease severity in sepsis, is a recognized driver of thromboinflammation and a potential therapeutic target. In sepsis, plasma cfDNA is mostly derived from neutrophil extracellular trap (NET) degradation. Proposed NET-directed therapeutic strategies include preventing NET formation or accelerating NET degradation. However, NET digestion liberates pathogens and releases cfDNA that promote thrombosis and endothelial cell injury. We propose an alternative strategy of cfDNA and NET stabilization with chemokine platelet factor 4 (PF4, CXCL4). We previously showed that human PF4 (hPF4) enhances NET-mediated microbial entrapment. We now show that hPF4 interferes with thrombogenicity of cfDNA and NETs by preventing their cleavage to short-fragment and single-stranded cfDNA that more effectively activates the contact pathway of coagulation. In vitro, hPF4 also inhibits cfDNA-induced endothelial tissue factor surface expression and von Willebrand factor release. In vivo, hPF4 expression reduced plasma thrombin-antithrombin (TAT) levels in animals infused with exogenous cfDNA. Following lipopolysaccharide challenge, Cxcl4-/- mice had significant elevation in plasma TAT, cfDNA, and cystatin C levels, effects prevented by hPF4 infusion. These results show that hPF4 interacts with cfDNA and NETs to limit thrombosis and endothelial injury, an observation of potential clinical benefit in the treatment of sepsis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.