A role for adhesion and degranulation-promoting adapter protein in collagen-induced platelet activation mediated via integrin α(2) ß(1).
J Thromb Haemost
; 10(2): 268-77, 2012 Feb.
Article
en En
| MEDLINE
| ID: mdl-22103309
ABSTRACT
BACKGROUND:
Collagen-induced platelet activation is a key step in the development of arterial thrombosis via its interaction with the receptors glycoprotein (GP)VI and integrin α(2) ß(1) . Adhesion and degranulation-promoting adapter protein (ADAP) regulates α(IIb) ß(3) in platelets and α(L) ß(2) in T cells, and is phosphorylated in GPVI-deficient platelets activated by collagen.OBJECTIVES:
To determine whether ADAP plays a role in collagen-induced platelet activation and in the regulation and function of α(2) ß(1).METHODS:
Using ADAP(-/-) mice and synthetic collagen peptides, we investigated the role of ADAP in platelet aggregation, adhesion, spreading, thromboxane synthesis, and tyrosine phosphorylation. RESULTS ANDCONCLUSIONS:
Platelet aggregation and phosphorylation of phospholipase Cγ2 induced by collagen were attenuated in ADAP(-/-) platelets. However, aggregation and signaling induced by collagen-related peptide (CRP), a GPVI-selective agonist, were largely unaffected. Platelet adhesion to CRP was also unaffected by ADAP deficiency. Adhesion to the α(2) ß(1) -selective ligand GFOGER and to a peptide (III-04), which supports adhesion that is dependent on both GPVI and α(2) ß(1), was reduced in ADAP(-/-) platelets. An impedance-based label-free detection technique, which measures adhesion and spreading of platelets, indicated that, in the absence of ADAP, spreading on GFOGER was also reduced. This was confirmed with non-fluorescent differential-interference contrast microscopy, which revealed reduced filpodia formation in ADAP(-/-) platelets adherent to GFOGER. This indicates that ADAP plays a role in mediating platelet activation via the collagen-binding integrin α(2) ß(1). In addition, we found that ADAP(-/-) mice, which are mildly thrombocytopenic, have enlarged spleens as compared with wild-type animals. This may reflect increased removal of platelets from the circulation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plaquetas
/
Activación Plaquetaria
/
Colágeno
/
Integrina alfa2beta1
/
Proteínas Adaptadoras Transductoras de Señales
Límite:
Animals
Idioma:
En
Revista:
J Thromb Haemost
Asunto de la revista:
HEMATOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido