Citrullinated fibrinogen shows defects in FPA and FPB release and fibrin polymerization catalyzed by thrombin.
Citrullinated fibrinogen shows defects in FPA and FPB release and fibrin polymerization catalyzed by thrombin.
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DOI：
10.1016/j.cca.2008.12.002
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发表时间：
2009-03
期刊：
影响因子：
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通讯作者：
N. Okumura;A. Haneishi;F. Terasawa
中科院分区：
文献类型：
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作者：
N. Okumura;A. Haneishi;F. Terasawa
目的研究瓜氨酸化纤维蛋白原在类风湿关节炎发病机制中的作用。方法利用兔骨骼肌肽酰精氨酸脱亚胺酶对重组纤维蛋白原进行瓜氨酸化修饰，分析瓜氨酸化纤维蛋白原的功能。即，进行凝血酶催化的纤维蛋白聚合和纤维蛋白肽释放、防止纤维蛋白溶酶消化以及凝血因子XIIIa催化的纤维蛋白或纤维蛋白原交联。通过抗改性瓜氨酸检测试剂盒检测Aα和Bβ链的强瓜氨酸和γ链的弱瓜氨酸。瓜氨酸化纤维蛋白原不通过凝血酶催化释放FPA或FPB，也不发生凝血酶刺激的纤维蛋白原转化为纤维蛋白。纤维蛋白原的瓜氨酸化不影响C-末端γ-链的3种功能，“a-孔”，低亲和力Ca结合和γ-γ crosslink. CONCLUSION我们的功能分析表明，没有凝血酶刺激的纤维蛋白原转化为纤维蛋白，因为瓜氨酸化的纤维蛋白原在凝血酶催化后不释放FPA或FPB。我们的研究结果和其他报告表明，瓜氨酸化纤维蛋白和纤维蛋白原存在于滑膜，可能都与RA的病理生理。
BACKGROUNDAntibody–antigen complexes formed by IgG autoantibodies against citrullinated proteins and citrullinated forms of the α- and β-chains of fibrin in rheumatoid synovial tissue play a key role in the pathophysiology of rheumatoid arthritis.METHODSRecombinant 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.RESULTSStrong citrullination of the Aα- and Bβ-chains and weak citrullination of the γ-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 γ-chain, “a-hole,” low affinity Ca binding, and γ–γ cross-linking.CONCLUSIONOur 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.