Characterization of the Hypercitrullination Reaction in Human Neutrophils and Other Leukocytes
Joint Authors
Zhou, Yebin
Di Pucchio, Tiziana
Sims, Gary P.
Mittereder, Nanette
Mustelin, Tomas
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-05-19
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Zhou, Yebin& Di Pucchio, Tiziana& Sims, Gary P.& Mittereder, Nanette& Mustelin, Tomas. 2015. Characterization of the Hypercitrullination Reaction in Human Neutrophils and Other Leukocytes. Mediators of Inflammation،Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1072194
Modern Language Association (MLA)
Zhou, Yebin…[et al.]. Characterization of the Hypercitrullination Reaction in Human Neutrophils and Other Leukocytes. Mediators of Inflammation No. 2015 (2015), pp.1-9.
https://search.emarefa.net/detail/BIM-1072194
American Medical Association (AMA)
Zhou, Yebin& Di Pucchio, Tiziana& Sims, Gary P.& Mittereder, Nanette& Mustelin, Tomas. Characterization of the Hypercitrullination Reaction in Human Neutrophils and Other Leukocytes. Mediators of Inflammation. 2015. Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1072194
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1072194