Citrullinated fibrinogen shows defects in FPA and FPB release and fibrin polymerization catalyzed by thrombin.
BACKGROUND
Antibody-antigen complexes formed by IgG autoantibodies against citrullinated proteins and citrullinated forms of the alpha- and beta-chains of fibrin in rheumatoid synovial tissue play a key role in the pathophysiology of rheumatoid arthritis.


METHODS
Recombinant fibrinogen was citrullinated by rabbit skeletal muscle peptidylarginine deiminase so that we could analyze the function of citrullinated fibrinogen. Namely, thrombin-catalyzed fibrin polymerization and fibrinopeptide release, protection against plasmin digestion, and factor XIIIa-catalyzed cross-linking of fibrin or fibrinogen were performed.


RESULTS
Strong citrullination of the Aalpha- and Bbeta-chains and weak citrullination of the gamma-chain were detected by an anti-modified citrulline detection kit. Citrullinated fibrinogen did not release FPA or FPB by thrombin catalyzation and no thrombin-stimulated conversion of fibrinogen into fibrin occurred. The citrullination of fibrinogen did not affect the 3 functions of the C-terminal gamma-chain, "a-hole," low affinity Ca binding, and gamma-gamma cross-linking.


CONCLUSIONS
Our functional analyses demonstrated that no thrombin-stimulated conversion of fibrinogen into fibrin occurred, because citrullinated fibrinogen did not release FPA or FPB after thrombin catalyzation. Our results and those of other reports suggest that citrullinated fibrin and fibrinogen are present in the synovium and might both be associated with the pathophysiology of RA.
Okumura
Nobuo
N
Department of Biomedical Laboratory Sciences, Laboratory of Clinical Chemistry, School of Health Sciences, Shinshu University, Japan. nobuoku@gipac.shinshu-u.ac.jp
Haneishi
Ayumi
A
Terasawa
Fumiko
F
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002384:Catalysis; D002956:Citrulline / Q000737:chemistry / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D005344:Fibrinopeptide A / Q000378:metabolism*; D005345:Fibrinopeptide B / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D013917:Thrombin / Q000378:metabolism*
D005344:Fibrinopeptide A; D002956:Citrulline; D005345:Fibrinopeptide B; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin