Contact activation-induced complex formation between complement factor H and coagulation factor XIIa.
J Thromb Haemost
; 18(4): 876-884, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-31984663
ABSTRACT
BACKGROUND:
The complement and coagulation systems share an evolutionary origin with many components showing structural homology. Certain components, including complement factor H (FH) and coagulation factor XII (FXII), have separately been shown to have auxiliary activities across the two systems.OBJECTIVES:
The interaction between FXII and FH was investigated.METHODS:
Using enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) complex formation between different FXII forms and FH was investigated. The presence of α-FXIIaFH complexes upon contact activation in plasma was evaluated by ELISA and immunoprecipitation.RESULTS:
We identified and characterized a direct interaction between the components and demonstrated that among different forms of FXII, only the activated α-FXIIa formed complexes with FH, with an apparent binding strength Kd of 34 ± 9 nmol/L. The complex formation involved the kringle domain of the heavy chain of FXII. C1-inhibitor induced inhibition of α-FXIIa did not alter the binding of α-FXIIa toward FH. We further demonstrated the presence of α-FXIIaFH complexes in normal human plasma upon contact activation, indicating formation of α-FXIIaFH complexes as a consequence of α-FXIIa generation. Complex formation between α-FXIIa and FH was also assessed in hereditary angioedema (HAE) patients with C1-inhibitor deficiency as well as rheumatoid arthritis (RA) patients with high levels of anti-cyclic citrullinated peptide (anti-CCP) upon contact activation. We observed elevated levels of α-FXIIaFH complexes in HAE patients, and equal levels of complexes in RA patients and healthy individuals upon contact activation.CONCLUSION:
A direct interaction between α-FXIIa and FH is demonstrated. Our findings represent a new crosstalk between these systems, potentially important in the onset and pathology of inflammatory vascular diseases.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator XIIa
/
Fator H do Complemento
/
Angioedemas Hereditários
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article