ArticleMediators of inflammation2015
Characterization of the Hypercitrullination Reaction in Human Neutrophils and Other Leukocytes.
Article in Mediators of inflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- NLRP3 inflammasome promotes PAD2/PAD4 release and protein citrullination in rheumatoid arthritis.Communications biology · 2026Article
- Differential histone tail citrullination by PAD Enzymes observed via NMR spectroscopy.bioRxiv : the preprint server for biology · 2026Article
- Evidence of membranolytic targeting and intracellular citrullination in neutrophils isolated from patients with rheumatoid arthritis.Scientific reports · 2024Article
- Peptidylarginine deiminase 2 citrullinates MZB1 and promotes the secretion of IgM and IgA.Frontiers in immunology · 2023Article
- Microbial pathways to subvert host immunity generate citrullinated neoantigens targeted in rheumatoid arthritis.Current opinion in structural biology · 2022Review
- HJACC. Basic to translational science · 2022Article
- Citrullination and PAD Enzyme Biology in Type 1 Diabetes - Regulators of Inflammation, Autoimmunity, and Pathology.Frontiers in immunology · 2021Review
- Deimination, Intermediate Filaments and Associated Proteins.International journal of molecular sciences · 2020Review
- Citrullination Alters the Antiviral and Immunomodulatory Activities of the Human Cathelicidin LL-37 During Rhinovirus Infection.Frontiers in immunology · 2020Article
- Autoantibodies against citrullinated serum albumin in patients with rheumatoid arthritis.Journal of translational autoimmunity · 2019Article
- Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes.International journal of molecular sciences · 2019Article
- Cutting Edge: Protein Arginine Deiminase 2 and 4 Regulate NLRP3 Inflammasome-Dependent IL-1β Maturation and ASC Speck Formation in Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Release of active peptidylarginine deiminase into the circulation during acute inflammation induced by coronary artery bypass surgery.Journal of inflammation research · 2019Article
- Evidence for a direct link between PAD4-mediated citrullination and the oxidative burst in human neutrophils.Scientific reports · 2018Article
- Perspective on Protein Arginine Deiminase Activity-Bicarbonate Is a pH-Independent Regulator of Citrullination.Frontiers in immunology · 2018Article
- The effect of triclosan on posttranslational modification of proteins through citrullination and carbamylation.Clinical oral investigations · 2018Article
- Chronic neutropenia in LGL leukemia and rheumatoid arthritis.Hematology. American Society of Hematology. Education Program · 2017Review
- Spontaneous Secretion of the Citrullination Enzyme PAD2 and Cell Surface Exposure of PAD4 by Neutrophils.Frontiers in immunology · 2017Article
- Citrullination in Rheumatoid Arthritis-A Process Promoted by Neutrophil Lysis?Rambam Maimonides medical journal · 2016Review
- Historical observations contributing insights on etiopathogenesis of rheumatoid arthritis and role of rheumatoid factor.The Journal of experimental medicine · 2016Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autoantibodies against citrullinated proteins are diagnostic for rheumatoid arthritis. However, the molecular mechanisms driving protein citrullination in patients with rheumatoid arthritis remain poorly understood. Using two independent western blotting methods, we report that agents that trigger a sufficiently large influx of extracellular calcium ions induced a marked citrullination of multiple proteins in human neutrophils, monocytes, and, to a lesser extent, T lymphocytes and natural killer cells, but not B lymphocytes or dendritic cells. This response required 250-1,000 μM extracellular calcium and was prevented by EDTA. Other neutrophil activating stimuli, such as formyl-peptides, GM-CSF, IL-6, IL8, TNFα, or phorbol ester, did not induce any detectable increase in protein citrullination, suggesting that receptor-induced calcium mobilization is insufficient to trigger hypercitrullination. We conclude that loss of membrane integrity and subsequent influx of high levels of calcium, which can be triggered by perforin released from cytotoxic cells or complement mediated formation of membrane attack complexes in the joints of rheumatoid arthritis patients, are sufficient to induce extensive protein citrullination in immune cells, notably neutrophils. This mechanism may provide the citrullinated autoantigens that drive autoimmunity in this devastating disease.
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