title: Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9), a biomarker for various pathological conditions, is produced in post-blood collection by fibrinolysis and coagulation factors.
abstract: BACKGROUND
  Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9) is a new serum biomarker for chronic hepatitis that was discovered by proteomics analysis. Previous studies have shown that FIC5.9 is derived from the C-terminal region of fibrinogen alpha chain and the serum levels of FIC5.9 decrease in chronic hepatitis. It also have been reported that FIC5.9 cannot be detected in the blood stream of the systemic circulation and it is released from fibrinogen during blood clotting in collecting tube. However, the mechanism of FIC5.9 releasing from fibrinogen is unclear.
  
  
  METHODS
  We formulated a hypothesis that FIC5.9 is released by enzymes that are activated by post-blood collection and may be coagulation and fibrinolysis factors. In this study, we analyzed the mechanisms of FIC5.9 releasing from fibrinogen in healthy blood.
  
  
  RESULTS
  Our analysis showed that thrombin acts as an initiator for FIC5.9 releasing, and that mainly plasmin cleaves N-terminal end of FIC5.9 and neutrophil elastase cleave C-terminal end of FIC5.9.
  
  
  CONCLUSIONS
  FIC5.9 reflects minute changes in coagulation and fibrinolysis factors and may be associated with pathological conditions.
authors.affiliation: Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan ; R&D Department, Nittobo Medical Co., Ltd., Koriyama, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kikuchi
authors.affiliation: Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Motoi
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kuga
authors.affiliation: Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Tsuchida
authors.affiliation: Department of Physics, School of Science, Kitasato University, Sagamihara, Kanagawa Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Satoh
authors.affiliation: R&D Department, Nittobo Medical Co., Ltd., Koriyama, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Noda
authors.affiliation: Department of Physics, School of Science, Kitasato University, Sagamihara, Kanagawa Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kodera
authors.affiliation: Laboratory of Proteome Research, National Institute of Biomedical Innovation, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.affiliation: Division of Clinical Mass Spectrometry and Clinical Genetics, Chiba University Hospital, Chiba, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
keywords:  Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9); Biomarker; Coagulation; Fibrinogen; Hepatitis; Plasmin; Thrombin