ArticleBlood2017
In vitro activation of coagulation by human neutrophil DNA and histone proteins but not neutrophil extracellular traps.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
146 citing papers in PubMed, 1 synthesis or guideline pooled it, 238 citations in OpenAlex.
- In vitro induction of NETosis: Comprehensive live imaging comparison and systematic review.PloS one · 2017Pooled it
- The Impact of Bariatric Surgery on Obesity-Associated NETosis, Immune Modulation, and Cardiovascular Risk Reduction.Obesity surgery · 2026Review
- NET-mediated immunothrombosis in ischemic stroke: pathobiology, biomarkers, and therapeutic targeting.Thrombosis journal · 2026Review
- Review
- Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones.Materials today. Bio · 2026Review
- Mechanobiology of cancer-associated thrombosis: from molecular mechanisms to therapeutic innovation.Journal of nanobiotechnology · 2026Review
- A Neutrophil-like Cell Model as Substitute for Human Neutrophils in NETs and Thrombosis Research.Cells · 2026Article
- Plasma Proteomic Profile of Chemotherapy-Induced Severe Neutropenia: A Pilot Discovery Phase Study.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Targeting Neutrophil Extracellular Traps: A New Strategy for the Treatment of Acute Ischemic Stroke Based on Thrombolysis Resistance.Seminars in thrombosis and hemostasis · 2026Review
- Sivelestat sodium mitigates lung injury post-acute pulmonary embolism by inhibiting NE-SPP1 neutrophil recruitment and restoring redox balance.Scientific reports · 2026Article
- Cationic nanoparticles with disrupting neutrophil extracellular traps inhibit the progression of head and neck squamous cell carcinoma.Frontiers in cell and developmental biology · 2026Article
- The role of neutrophil extracellular traps in antiphospholipid syndrome.Frontiers in immunology · 2026Review
- Cell-free DNA in sepsis: from molecular insights to clinical management.Military Medical Research · 2025Review
- Tandem ssDNA in neutrophil extracellular traps binds thrombin and regulates immunothrombosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Disseminated intravascular coagulation.Journal of intensive care · 2025Review
- The NET-DNA-CCDC25 inhibitor di-Pal-MTO suppresses tumor progression and promotes the innate immune response.Cellular & molecular immunology · 2025Article
- From Circulating Biomarkers to Polymorphic Variants: A Narrative Review of Challenges in Thrombophilia Evaluation.Journal of clinical medicine · 2025Review
- Article
- The Crosstalk Between NETs and the Complement Cascade: An Overview in Nephrological Autoimmune Disease.International journal of molecular sciences · 2025Review
- Neutrophil Extracellular Traps in Atherosclerosis: Research Progress.International journal of molecular sciences · 2025Review
86 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
NETosis is a physiologic process in which neutrophils release their nuclear material in the form of neutrophil extracellular traps (NETs). NETs have been reported to directly promote thrombosis in animal models. Although the effects of purified NET components including DNA, histone proteins, and neutrophil enzymes on coagulation have been characterized, the mechanism by which intact NETs promote thrombosis is largely unknown. In this study, human neutrophils were stimulated to produce NETs in platelet-free plasma (PFP) or in buffer using phorbol myristate actetate or calcium ionophore. DNA and histone proteins were also separately purified from normal human neutrophils and used to reconstitute chromatin using a salt-gradient dialysis method. Neutrophil stimulation resulted in robust NET release. In recalcified PFP, purified DNA triggered contact-dependent thrombin generation (TG) and amplified TG initiated by low concentrations of tissue factor. Similarly, in a buffer milieu, DNA initiated the contact pathway and amplified thrombin-dependent factor XI activation. Recombinant human histones H3 and H4 triggered TG in recalcified human plasma in a platelet-dependent manner. In contrast, neither intact NETs, reconstituted chromatin, individual nucleosome particles, nor octameric core histones reproduced any of these procoagulant effects. We conclude that unlike DNA or individual histone proteins, human intact NETs do not directly initiate or amplify coagulation in vitro. This difference is likely explained by the complex histone-histone and histone-DNA interactions within the nucleosome unit and higher-order supercoiled chromatin leading to neutralization of the negative charges on polyanionic DNA and modification of the binding properties of individual histone proteins.
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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.