Protein C supports platelet binding and activation under flow: role of glycoprotein Ib and apolipoprotein E receptor 2.
J Thromb Haemost
; 6(6): 995-1002, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18489431
ABSTRACT
BACKGROUND:
Activated protein C (APC) regulates thrombin generation and inhibits apoptosis. Endothelial protein C receptor (EPCR)-bound protein C is activated by thrombomodulin-bound thrombin. APC inactivates coagulation factors (F)Va/VIIIa and generates cytoprotective signaling downstream of protease-activated receptor-1 (PAR-1). Binding of APC to EPCR both modifies and induces PAR-1 signaling, but it is unknown if protein C interacts with cells in an alternative manner.AIM:
To determine whether platelets possess receptors for protein C that can generate intracellular signals.RESULTS:
Immobilized protein C or APC supported platelet adhesion, lamellipodia formation and elevation of intracellular Ca(2+). Adhesion of platelets to protein C or APC was inhibited by soluble recombinant apolipoprotein E receptor 2' (ApoER2') and by receptor-associated protein (RAP), an inhibitor of the low-density lipoprotein receptor family. Under shear, surface-bound protein C supported platelet adhesion and aggregation in a glycoprotein (GP)Ibalpha-dependent manner, and adhesion of platelets to immobilized protein C was abrogated by the addition of soluble forms of ApoER2' or RAP. APC bound to purified recombinant ApoER2' or GPIbalpha.CONCLUSIONS:
Our data demonstrate that activation of platelets with rapid intracellular signaling caused by binding to immobilized protein C or APC occurs via mechanisms that require ApoER2 and GPIbalpha and that APC directly binds to purified ectodomains of the receptors ApoER2 and GPIbalpha. These findings imply that protein C and APC may directly promote cell signaling in other cells by binding to ApoER2 and/or GPIbalpha.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Proteína C
/
Regulação da Expressão Gênica
/
Receptores de Lipoproteínas
/
Complexo Glicoproteico GPIb-IX de Plaquetas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Thromb Haemost
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos