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. 2016 Oct 7:13:27.
doi: 10.1186/s12014-016-9129-6. eCollection 2016.

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

Wataru Kikuchi  1 , Motoi Nishimura  2 , Takahisa Kuga  3 , Sachio Tsuchida  2 , Tatsuya Saito  4 , Mamoru Satoh  2 , Kenta Noda  5 , Yoshio Kodera  4 , Takeshi Tomonaga  6 , Fumio Nomura  7
Affiliations

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

Wataru Kikuchi et al. Clin Proteomics. .

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.

Conclusion: FIC5.9 reflects minute changes in coagulation and fibrinolysis factors and may be associated with pathological conditions.

Keywords: Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9); Biomarker; Coagulation; Fibrinogen; Hepatitis; Plasmin; Thrombin.

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Figures

Fig. 1
Fig. 1
Fibrinogen and FIC5.9 region (a). A model of FIC5.9 synthesis (b). FIC5.9 is released from fibrinogen during the process of blood coagulation [8]. FIC5.9 is not found in blood plasma and only detected in serum after blood clotting
Fig. 2
Fig. 2
Sequences of fibrinogen alpha chain and FIC5.9. The mature alpha chain is indicated by a grey shadow. The FIC5.9 sequence (amino acids 576–629) is underlined
Fig. 3
Fig. 3
Cleavage site mapping of thrombin, plasmin and neutrophil elastase in FIC5.9 surrounding regions. Cleavage sites are indicated with scissors, depending on the number of peptides identified by LC–MS/MS analysis. Identified peptide sequence information is shown in Additional file 2
Fig. 4
Fig. 4
Analysis of time course of FIC5.9 releasing with thrombin spiked/inhibited (a), plasmin spiked/inhibited (b), or neutrophil elastase inhibited (c) serum collection tubes. The relative amount of FIC5.9 was measured by FIC5.9 ELISA. Statistical comparison of silica-coated tube versus enzyme-spiked tube (asterisk), or inhibitor spiked tube (dagger symbol) was performed as described in the “Methods” section
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