In vivo relevance for platelet glycoprotein Ibalpha residue Tyr276 in thrombus formation.
J Thromb Haemost
; 6(4): 684-91, 2008 Apr.
Article
en En
| MEDLINE
| ID: mdl-18339097
ABSTRACT
BACKGROUND:
Platelet glycoprotein (GP) Ib-IX-V supports platelet adhesion on damaged vascular walls by binding to von Willebrand factor (VWF). For several decades it has been recognized that the alpha-subunit of GP (GPIbalpha) also binds thrombin but the physiological relevance, if any, of this interaction was unknown. Previous studies have shown that a sulfated tyrosine 276 (Tyr276) is essential for thrombin binding to GPIbalpha.OBJECTIVES:
This study investigated the in vivo relevance of GPIbalpha residue Tyr276 in hemostasis and thrombosis.METHODS:
Transgenic mouse colonies expressing the normal human GPIbalpha subunit or a mutant human GPIbalpha containing a Phe substitution for Tyr276 (hTg(Y276F)) were generated. Both colonies were bred to mice devoid of murine GPIbalpha.RESULTS:
Surface-expressed GPIbalpha levels and platelet counts were similar in both colonies. hTg(Y276F) platelets were significantly impaired in binding alpha-thrombin but displayed normal binding to type I fibrillar collagen and human VWF in the presence of ristocetin. In vivo thrombus formation as a result of chemical damage (FeCl(3)) demonstrated that hTg(Y276F) mice have a delayed time to occlusion followed by unstable blood flow indicative of embolization. In models of laser-induced injury, thrombi developing in hTg(Y276F) animals were also less stable.CONCLUSIONS:
The results demonstrate that GPIbalpha residue Tyr276 is physiologically important, supporting stable thrombus formation in vivo.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tirosina
/
Coagulación Sanguínea
/
Complejo GPIb-IX de Glicoproteína Plaquetaria
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Thromb Haemost
Asunto de la revista:
HEMATOLOGIA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos