title: Free factor XIII activation peptide (fAP-FXIII) is a regulator of factor XIII activity via factor XIII-B.
abstract: In a factor XIIIa (FXIIIa) generation assay with recombinant FXIII-A2 (rFXIII-A2 ) 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 factorXIII-B2 (rFXIII-B2 ) restored the characteristics of the FXIIIa generation parameters (AUC, TTP and CP) to those observed for plasma FXIII (FXIII-A2 B2 ). FXIII-A2 B2 reconstituted from rFXIII-A2 and rFXIII-B2 showed a similar effect on AUC, TTP and CP in the presence of fAP-FXII as observed for plasma FXIII-A2 B2 , 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 FXIIIa activity development of thrombin-cleaved rFXIII-A2 (rFXIII-A2 ') also excluding direct inhibition of FXIIIa. However, FXIIIa activity development of FXIII-A2 'B2 was inhibited in a concentration-dependent manner by fAP-FXIII, indicating that an interaction between AP-FXIII and FXIII-B2 contributes to the overall stability of FXIII-A2 'B2 . In addition to its well-known role, FXIII-B also contributes to FXIII-A2 B2 stability or dissociation depending on fAP-FXIII and calcium concentrations.
authors.affiliation: Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Dodt
authors.affiliation: Zedira GmbH, Darmstadt, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Pasternack
authors.affiliation: Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Seitz
authors.affiliation: Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Volkers
mesh_terms: D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005176:Factor XIII / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011994:Recombinant Proteins; C061895:factor XIII activation peptide; C064015:factor XIII subunit A; D005176:Factor XIII; C054380:factor XIIIb; D013917:Thrombin
keywords: activated factor XIII; factor XIII; factor XIII potential; free activation peptide factor XIII; recombinant cellular factor XIII