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Ann Rheum Dis. 2004 Apr;63(4):373-81.

Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages.

Author information

1
Department of Biochemistry, University of Nijmegen, Nijmegen, The Netherlands. e.vossenaar@ncmls.kun.nl

Abstract

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.

PMID:
15020330
PMCID:
PMC1754951
[Indexed for MEDLINE]
Free PMC Article

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