Exploring the function of factor XIII free B subunit: Interactions with complement factors and a novel approach to identify potential binding partners.
Res Pract Thromb Haemost
; 6(5): e12766, 2022 Jul.
Article
in En
| MEDLINE
| ID: mdl-35873217
ABSTRACT
Background:
The factor XIII (FXIII)-B subunit has a critical function as a carrier protein to stabilize FXIII-A in plasma and supply it to its main substrate, fibrinogen. However, the function of the excess free FXIII-B circulating in plasma is still elusive.Objectives:
In the present study, we explored potential interactions of free FXIII-B with complement factors and searched for novel binding partners.Methods:
We tested for cofactor activity in the degradation of complement C3b and C4b and used ELISA- and surface plasmon resonance-based binding assays to investigate interactions between FXIII-B and complement components. We performed immunoprecipitation and mass spectrometry analysis to identify potential binding partners of free FXIII-B in freshly drawn plasma samples.Results:
FXIII-B did not exhibit cofactor activity in the degradation of C3b and C4b similar to factor H and C4b-binding protein, nor did it bind to complement factors to a relevant extent. Identification of proteins potentially binding to free FXIII-B revealed high interindividual variation. We confirmed α2-macroglobulin (α2MG) as a candidate, although direct interactions or functional effects remain to be validated.Conclusions:
Our study reveals that free FXIII-B has no direct role in regulating the complement system, despite a structural similarity to major complement regulators. Further studies are needed to validate α2MG as a binding partner and explore potential functional consequences of this binding.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Prognostic_studies
Language:
En
Journal:
Res Pract Thromb Haemost
Year:
2022
Type:
Article