Decreased sickle red blood cell adhesion to laminin by hydroxyurea is associated with inhibition of Lu/BCAM protein phosphorylation.
Blood
; 116(12): 2152-9, 2010 Sep 23.
Article
em En
| MEDLINE
| ID: mdl-20566895
ABSTRACT
Sickle cell disease is characterized by painful vaso-occlusive crises during which abnormal interactions between erythroid adhesion molecules and vessel-wall proteins are thought to play a critical role. Hydroxyurea, the only drug with proven benefit in sickle cell disease, diminishes these interactions, but its mechanism of action is not fully understood. We report that, under hydroxyurea, expression of the unique erythroid laminin receptor Lu/BCAM was increased, but red blood cell adhesion to laminin decreased. Because Lu/BCAM phosphorylation is known to activate cell adhesion to laminin, it was evaluated and found to be dramatically lower in hydroxyurea-treated patients. Analysis of the protein kinase A pathway showed decreased intracellular levels of the upstream effector cyclic adenosine monophosphate during hydroxyurea treatment. Using a cellular model expressing recombinant Lu/BCAM, we showed that hydroxyurea led to decreased intracellular cyclic adenosine monophosphate levels and diminished Lu/BCAM phosphorylation and cell adhesion. We provide evidence that hydroxyurea could reduce abnormal sickle red blood cell adhesion to the vascular wall by regulating the activation state of adhesion molecules independently of their expression level.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Moléculas de Adesão Celular
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Adesão Celular
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Eritrócitos Anormais
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Hidroxiureia
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Anemia Falciforme
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Sistema do Grupo Sanguíneo Lutheran
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França