Proteolysis of the endothelial cell protein C receptor by neutrophil proteinase 3.
J Thromb Haemost
; 5(5): 980-8, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17459006
ABSTRACT
BACKGROUND:
The endothelial cell protein C receptor (EPCR) presents protein C to the thrombinthrombomodulin complex on the endothelium of large vessels, and enhances the generation of activated protein C (APC) and activation of protease-activated receptor-1. A previous report has demonstrated binding of soluble (s) EPCR to activated neutrophils via surface proteinase 3 (PR3).METHODS:
We now report further characterization of this interaction. Activated neutrophils and purified PR3 both decrease endothelial cell (EC) surface EPCR, suggestive of its proteolysis.RESULTS:
When added to purified recombinant sEPCR, PR3 produced multiple cleavages, with early products including 20 kDa N-terminal and C-terminal (after Lys(176)) fragments. The binding of active site blocked PR3 to sEPCR was studied by surface plasmon resonance. Estimates of the K(D) of 18.5-102 nM were obtained with heterogeneous binding, suggestive of more than a single interaction site.CONCLUSIONS:
This work demonstrates PR3 binding to and proteolysis of EPCR and suggests a mechanism by which anticoagulant and cell protective pathways can be down-regulated during inflammation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Coagulação Sanguínea
/
Receptores de Superfície Celular
/
Mieloblastina
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article