ArticleThe Journal of biological chemistry2017
Activated protein C inhibits neutrophil extracellular trap formation
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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.
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Who cites it
62 citing papers in PubMed, 109 citations in OpenAlex.
- Trial
- Neutrophil Extracellular Traps in Wound Healing of Diabetes: Mechanisms, Inducers, and Therapeutic Implications.Mediators of inflammation · 2026Review
- A comprehensive insight into NETosis-extracellular vesicle crosstalk in autoimmune diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Lenvatinib-activated NDUFA4L2/IL33/PADI4 pathway induces neutrophil extracellular traps that inhibit cuproptosis in hepatocellular carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Endothelial Protein C Receptor: A Multifunctional Mediator in the Pathophysiology of Rheumatoid Arthritis.Cells · 2025Review
- Thrombomodulin: A key regulator of intravascular blood coagulation, fibrinolysis, and inflammation, and a treatment for disseminated intravascular coagulation.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- "The NET effect": Neutrophil extracellular traps-a potential key component of the dysregulated host immune response in sepsis.Critical care (London, England) · 2025Review
- Neutrophil extracellular traps in sepsis: trade-off between pros and cons.Burns & trauma · 2025Review
- Mac-1 blockade impedes adhesion-dependent neutrophil extracellular trap formation and ameliorates lung injury in LPS-induced sepsis.Frontiers in immunology · 2025Article
- Localization of Hemostasis Elements in Aspirated Coronary Thrombi at Different Stages of Evolution.International journal of molecular sciences · 2024Article
- Neutrophil extracellular traps in homeostasis and disease.Signal transduction and targeted therapy · 2024Review
- Platelets at the intersection of inflammation and coagulation in the APC-mediated response to myocardial ischemia/reperfusion injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Unraveling the differential mechanisms of revascularization promoted by MSCs & ECFCs from adipose tissue or umbilical cord in a murine model of critical limb-threatening ischemia.Journal of biomedical science · 2024Article
- Review
- Coagulation and Inflammation in COVID-19: Reciprocal Relationship between Inflammatory and Coagulation Markers.Annals of hematology · 2024Review
- Targeting Neutrophil Extracellular Trap Formation: Exploring Promising Pharmacological Strategies for the Treatment of Preeclampsia.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Thrombin Generation Assay in Antiphospholipid Antibodies Positive Subjects as a Personalized Thrombotic Risk Assessment: State of the Art and Perspectives.Current rheumatology reports · 2024Review
- Endothelial Protein C Receptor and Its Impact on Rheumatic Disease.Journal of clinical medicine · 2024Review
- Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review.Frontiers in immunology · 2024Review
- Recent advances in the role of neutrophils and neutrophil extracellular traps in acute pancreatitis.Clinical and experimental medicine · 2023Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Activated protein C (APC) is a multifunctional serine protease with anticoagulant, cytoprotective, and anti-inflammatory activities. In addition to the cytoprotective effects of APC on endothelial cells, podocytes, and neurons, APC cleaves and detoxifies extracellular histones, a major component of neutrophil extracellular traps (NETs). NETs promote pathogen clearance but also can lead to thrombosis; the pathways that negatively regulate NETosis are largely unknown. Thus, we studied whether APC is capable of directly inhibiting NETosis via receptor-mediated cell signaling mechanisms. Here, by quantifying extracellular DNA or myeloperoxidase, we demonstrate that APC binds human leukocytes and prevents activated platelet supernatant or phorbol 12-myristate 13-acetate (PMA) from inducing NETosis. Of note, APC proteolytic activity was required for inhibiting NETosis. Moreover, antibodies against the neutrophil receptors endothelial protein C receptor (EPCR), protease-activated receptor 3 (PAR3), and macrophage-1 antigen (Mac-1) blocked APC inhibition of NETosis. Select mutations in the Gla and protease domains of recombinant APC caused a loss of NETosis. Interestingly, pretreatment of neutrophils with APC prior to induction of NETosis inhibited platelet adhesion to NETs. Lastly, in a nonhuman primate model of
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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.