ArticleCell death discovery2018
Activated platelets induce MLKL-driven neutrophil necroptosis and release of neutrophil extracellular traps in venous thrombosis.
Article in Cell death discovery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
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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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.Nature reviews. Drug discovery · 2020Pooled it
- Skin graft surgery and its impact on platelet counts in Iranian burn patients: a non-randomized clinical trial.BMC surgery · 2024Trial
- Impact of Neutrophil Extracellular Traps on Clinical Outcome after Subarachnoid Hemorrhage: A Translational Narrative Review.Translational stroke research · 2026Review
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.Apoptosis : an international journal on programmed cell death · 2025Review
- Converging Molecular Mechanisms of Nucleated Cell Death Pathways and Procoagulant Platelet Formation.Cells · 2025Review
- Association of preoperative systemic inflammation with postoperative conduction block in TAVI patients.Frontiers in cardiovascular medicine · 2025Article
- Alterations in visible light exposure modulate platelet function and regulate thrombus formation.Journal of thrombosis and haemostasis : JTH · 2025Article
- Tetrahedral DNA Nanostructures as a Multifactorial Nanotherapeutic Platform for Deep Vein Thrombosis: Targeting Necroptosis, Oxidative Stress, and Inflammation.International journal of nanomedicine · 2025Article
- Acute lung injury: a view from the perspective of necroptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis: Current Knowledge and Future Perspectives.Current medical science · 2024Review
- Oxidative stress in acute pulmonary embolism: emerging roles and therapeutic implications.Thrombosis journal · 2024Review
- Necroptosis executioner MLKL plays pivotal roles in agonist-induced platelet prothrombotic responses and lytic cell death in a temporal order.Cell death and differentiation · 2023Article
- Progress in study on the final executor of necroptosis MLKL and its inhibitors.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Neutrophil extracellular traps mediate deep vein thrombosis: from mechanism to therapy.Frontiers in immunology · 2023Review
- Pathogenesis and Therapy of Coagulation Disorders in Severe Acute Pancreatitis.Journal of inflammation research · 2023Review
- Regulated necrosis pathways: a potential target for ischemic stroke.Burns & trauma · 2023Review
- Platelet-Neutrophil Association in NETs-Rich Areas in the Retrieved AIS Patient Thrombi.International journal of molecular sciences · 2022Article
- Neutrophil extracellular traps: from physiology to pathology.Cardiovascular research · 2022Review
- Catching a killer: Mechanisms of programmed cell death and immune activation in Amyotrophic Lateral Sclerosis.Immunological reviews · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Venous thromboembolic (VTE) disease, often manifesting as deep vein thrombosis or pulmonary embolism, involves clot formation consisting of blood cells and platelets locked in plasma protein and chromatin networks. The latter derives from neutrophil extracellular traps released by dying neutrophils; however, the molecular mechanisms of neutrophil death in VTE remains unknown. We speculated that mixed lineage kinase-like (MLKL)-driven neutrophil necroptosis contributes to VTE. Indeed, human inferior venous cava thrombus material stained positive for phosphorylated MLKL, the activated version of MLKL that executes necroptotic cell death. In mice, MLKL immunostaining showed co-localization of MLKL with citrullinated histone H3, a marker of neutrophil extracellular trap (NET) formation. These data provide indirect support for a role of MLKL-mediated necroptosis. As a functional proof, both the stabilizer of receptor-interacting protein kinase-1 (RIPK1) and necroptosis inhibitor necrostatin-1s as well as genetic deficiency of MLKL partially prevented clot formation upon inferior vena cava ligation in mice. In both experiments terminal deoxynucleotidyl transferase dUTP nick-end labeling, RIPK3, and citrullinated histone H3+ areas were markedly reduced within the remnant thrombus. In vitro, thrombin-activated platelets induced cell death and NET formation in human neutrophils, which was inhibited by necrostatin-1s treatment. Necrostatin-1s and necrosulfonamide also inhibited neutrophil-platelet aggregate formation induced by tumor necrosis factor-α but had no effect on platelet activation itself. We conclude that in VTE, activated platelets, and possibly other triggers, induce neutrophil necroptosis, a process contributing to clot formation by releasing chromatin in the extracellular space.
Identifiers
What OpenQuestion holds
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.