Activation of integrin alpha IIb beta 3 in the glycoprotein Ib-high population of a megakaryocytic cell line, CMK, by inside-out signaling.
J Thromb Haemost
; 2(1): 177-86, 2004 Jan.
Article
en En
| MEDLINE
| ID: mdl-14717982
Affinity/avidity state of integrin alpha IIb beta 3 is regulated by intracellular inside-out signaling. Although several megakaryocytic cell lines have been established, soluble ligand binding to alpha IIb beta 3 expressed in these cells by cellular agonists has not been demonstrated. We have re-examined agonist-induced alpha IIb beta 3 activation on megakaryocytic cell lines with a marker of the late stage of megakaryocytic differentiation, glycoprotein Ib (GPIb). Activation of alpha IIb beta 3 was assessed by PAC1 and soluble fibrinogen binding to the cells. We found that alpha IIb beta 3 expressed in CMK cells with high GPIb expression was activated by a phorbor ester, phorbol myristate acetate (PMA). Although the population of the GPIbhigh cells was <0.5% of the total cells, incubation with a nucleoside analog, ribavirin, efficiently increased the PMA-reactive GPIbhigh cells. Not only PMA but also a calcium ionophore, A23187, induced alpha IIb beta 3 activation, and PMA and A23187 had an additive effect on alpha IIb beta 3 activation. Ligand binding to the activated alpha IIb beta 3 in the GPIbhigh CMK cells is totally abolished by an alpha IIb beta 3-specific antagonist, and inhibited by wortmannin, cytochalasin-D and prostaglandin E1, and the effects of these inhibitors on alpha IIb beta 3 activation in the GPIbhigh CMK cells were compatible with those in platelets. We have also demonstrated that the ribavirin-treated CMK cells express PKC-alpha, -beta, -delta and -theta, and suggested that PKC-alpha and/or -beta appear to be responsible for PMA-induced activation of alpha IIb beta 3 in CMK cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Megacariocitos
/
Complejo GPIIb-IIIa de Glicoproteína Plaquetaria
/
Complejo GPIb-IX de Glicoproteína Plaquetaria
Límite:
Humans
Idioma:
En
Revista:
J Thromb Haemost
Asunto de la revista:
HEMATOLOGIA
Año:
2004
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido