title: Citrullinated fibrinogen inhibits thrombin-catalysed fibrin polymerization.
abstract: Citrullination is the post-translational modification of arginine residues by peptidylarginine deiminases (PADIs). Fibrinogen is one substrate of PADIs under physiological conditions. Fibrinogen is an important factor for blood coagulation and inducing inflammation. The citrullinated form of fibrinogen appears in rheumatoid arthritis synovial tissue together with the production of autoantibodies that target self-peptides containing citrulline. However, whether the function of fibrinogen changes after citrullination remains unclear. We found that citrullinated fibrinogen markedly impairs the function of thrombin-catalysed fibrin polymerization and also inhibits fibrin formation. Increased citrullinated fibrinogen might thus affect the balance between coagulation and fibrinolysis and alter antigenicity under physiological conditions. These data suggest that citrullination of proteins could physiologically change functions and subsequently generate pro-inflammatory conditions and autoimmune reactions.
authors.affiliation: Daiichi-Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Nakayama-Hamada
authors.forename: Akari
authors.initials: A
authors.lastname: Suzuki
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Furukawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D001120:Arginine / Q000737:chemistry; D001777:Blood Coagulation; D002384:Catalysis; D002956:Citrulline / Q000737:chemistry*; D004492:Edetic Acid / Q000737:chemistry; D005337:Fibrin / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D007700:Kinetics; D010455:Peptides / Q000737:chemistry; D013379:Substrate Specificity; D013917:Thrombin / Q000737:chemistry*; D013997:Time Factors
chemical_list: D010455:Peptides; D002956:Citrulline; D005337:Fibrin; D005340:Fibrinogen; D001120:Arginine; D004492:Edetic Acid; D013917:Thrombin