ArticlePloS one2021
Neutrophil stimulation with citrullinated histone H4 slows down calcium influx and reduces NET formation compared with native histone H4.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Circulating Nucleosomes are Elevated in Trauma Patients with Venous Thromboembolism: A Prospective Case-Cohort Study.Shock (Augusta, Ga.) · 2026Article
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- A feedback loop sustaining neutrophil extracellular trap formation involves S100 proteins, histones, TLR2 and RAGE, and is restrained by albumin.Frontiers in immunology · 2026Article
- Extracellular vimentin is a damage-associated molecular pattern protein serving as an agonist of TLR4 in human neutrophils.Cell communication and signaling : CCS · 2025Article
- Fantastic proteins and where to find them - histones, in the nucleus and beyond.Journal of cell science · 2024Review
- Neutrophil Extracellular Traps in Tumors and Potential Use of Traditional Herbal Medicine Formulations for Its Regulation.International journal of nanomedicine · 2024Review
- Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review.Frontiers in immunology · 2024Review
- Neutrophil extracellular traps in the pathology of cancer and other inflammatory diseases.Physiological reviews · 2023Review
- Liang-Ge Decoction Ameliorates Coagulation Dysfunction in Cecal Ligation and Puncture-Induced Sepsis Model Rats through Inhibiting PAD4-Dependent Neutrophil Extracellular Trap Formation.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Neutrophil Extracellular Traps as an Exacerbating Factor in Bacterial Pneumonia.Infection and immunity · 2022Article
- The role of extracellular traps in ischemia reperfusion injury.Frontiers in immunology · 2022Review
- Histones: The critical players in innate immunity.Frontiers in immunology · 2022Review
- Damage associated molecular patterns and neutrophil extracellular traps in acute pancreatitis.Frontiers in cellular and infection microbiology · 2022Review
- Neutrophil extracellular traps and complications of liver transplantation.Frontiers in immunology · 2022Review
- Crosstalk between B cells and neutrophils in rheumatoid arthritis.Immunology · 2021Review
- Neutrophil Extracellular Traps (NETs) and Hypercoagulability in Plasma Cell Dyscrasias-Is This Phenomenon Worthy of Exploration?Journal of clinical medicine · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Peptidylarginine deiminase 4 (PAD4) catalyzes posttranslational modification of many target proteins through converting protein arginine or mono-methylarginine to citrulline. Neutrophil extracellular trap (NET) formation is the most dramatic manifestation of PAD4-mediated hypercitrullination reaction in neutrophils, which is characterized by the release of nuclear chromatin to form a chromatin network in the extracellular space. Histones H4, one of the major protein components of chromatin, is released into the extracellular space during sepsis, trauma, and ischemia-reperfusion injury and can also be released during the process of NET formation, along with its citrullinated form. The present study showed that histone H4 can induce NET formation in a calcium and PAD4 dependent manner. Histone H4 caused permeabilization of the neutrophil membrane and sustained rise in intracellular calcium that is necessary for activation of PAD4. In comparison, citrullinated histone H4 induced less calcium influx compared with its native form, leading to reduced NET formation. These studies suggest that citrullinated histone H4 could serve as a brake in the pathology of NETs, slowing down the vicious circle between histone H4 and NETs.
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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.