Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages.
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Publication year
2004Source
Annals of the Rheumatic Diseases, 63, 4, (2004), pp. 373-81ISSN
Publication type
Article / Letter to editor
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Organization
Biomolecular Chemistry
Rheumatology
Urology
Biochemistry (UMC)
Journal title
Annals of the Rheumatic Diseases
Volume
vol. 63
Issue
iss. 4
Page start
p. 373
Page end
p. 81
Subject
Bio-Molecular Chemistry; UMCN 4.2: Chronic inflammation and autoimmunityAbstract
BACKGROUND: Antibodies directed to proteins containing the non-standard amino acid citrulline, are extremely specific for rheumatoid arthritis (RA). Peptidylcitrulline can be generated by post-translational conversion of arginine residues. This process, citrullination, is catalysed by a group of calcium dependent peptidylarginine deiminase (PAD) enzymes. OBJECTIVE: To investigate the expression and activity of four isotypes of PAD in peripheral blood and synovial fluid cells of patients with RA. RESULTS: The data presented here show that citrullination of proteins by PAD enzymes is a process regulated at three levels: transcription-in peripheral blood PAD2 and PAD4 mRNAs are expressed predominantly in monocytes; PAD4 mRNA is not detectable in macrophages, translation-translation of PAD2 mRNA is subject to differentiation stage-specific regulation by its 3' UTR, and activation-the PAD proteins are only activated when sufficient Ca(2+) is available. Such high Ca(2+) concentrations are normally not present in living cells. In macrophages, which are abundant in the inflamed RA synovium, vimentin is specifically citrullinated after Ca(2+) influx. CONCLUSION: PAD2 and PAD4 are the most likely candidate PAD isotypes for the citrullination of synovial proteins in RA. Our results indicate that citrullinated vimentin is a candidate autoantigen in RA.
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- Academic publications [238430]
- Electronic publications [122512]
- Faculty of Medical Sciences [90359]
- Faculty of Science [34989]
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