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Free factor XIII activation peptide ( fAP ‐ FXIII ) is a regulator of factor XIII activity via factor XIII ‐B
Author(s) -
Dodt Johannes,
Pasternack Ralf,
Seitz Rainer,
Volkers Peter
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13835
Subject(s) - peptide , regulator , chemistry , biochemistry , gene
Summary In a factor XIII a ( FXIII a) generation assay with recombinant FXIII ‐A 2 ( rFXIII ‐A 2 ) free FXIII activation peptide ( fAP ‐ FXII ) prolonged the time to peak ( TTP ) but did not affect the area under the curve ( AUC ) or concentration at peak ( CP ). Addition of recombinant factor XIII ‐B 2 ( rFXIII ‐B 2 ) restored the characteristics of the FXIII a generation parameters ( AUC , TTP and CP ) to those observed for plasma FXIII ( FXIII ‐A 2 B 2 ). FXIII ‐A 2 B 2 reconstituted from rFXIII ‐A 2 and rFXIII ‐B 2 showed a similar effect on AUC , TTP and CP in the presence of fAP ‐ FXII as observed for plasma FXIII ‐A 2 B 2 , indicating a role for FXIII ‐B in this observation. An effect of fAP ‐ FXIII on thrombin, the proteolytic activator of FXIII , was excluded by thrombin generation assays and clotting experiments. In a purified system, fAP ‐ FXIII did not interfere with the FXIII a activity development of thrombin‐cleaved rFXIII ‐A 2 ( rFXIII ‐A 2 ′) also excluding direct inhibition of FXIII a. However, FXIII a activity development of FXIII ‐A 2 ′B 2 was inhibited in a concentration‐dependent manner by fAP ‐ FXIII , indicating that an interaction between AP ‐ FXIII and FXIII ‐B 2 contributes to the overall stability of FXIII ‐A 2 ′B 2 . In addition to its well‐known role, FXIII ‐B also contributes to FXIII ‐A 2 B 2 stability or dissociation depending on fAP ‐ FXIII and calcium concentrations.