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

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.

journal_name

Ann Rheum Dis

authors

Vossenaar ER,Radstake TR,van der Heijden A,van Mansum MA,Dieteren C,de Rooij DJ,Barrera P,Zendman AJ,van Venrooij WJ

doi

10.1136/ard.2003.012211

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

373-81

issue

4

eissn

0003-4967

issn

1468-2060

journal_volume

63

pub_type

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