HIV protease inhibitor therapy reverses neutrophil apoptosis in AIDS patients by direct calpain inhibition.
Apoptosis
; 11(5): 781-7, 2006 May.
Article
en En
| MEDLINE
| ID: mdl-16528469
ABSTRACT
The reduction of neutrophils apoptosis is one of the main non-virological effects of protease inhibitor (PI) therapy. We explore here whether this may be due to the cross-inhibition of calpain, an important non-virological target of PI in vitro. We found that the high basal level of neutrophils apoptosis in AIDS patients is strictly related to an increased intracellular calpain activity. Both alterations disappear after PI treatment, with apoptosis and calpain going back to normal levels after 3 months of PI therapy, independently of a proficient antiviral effect. PI drugs exerted a similar antiapoptotic and anticalpain effects on neutrophils in ex vivo experiments strikingly, the effects were mimicked by commercially available calpain inhibitors. This study shows, for the first time, that apoptosis of neutrophils in AIDS patients is mediated by calpain, and that neutrophil survival in PI treated AIDS patients is a non virological effect due to calpain inhibition.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calpaína
/
Síndrome de Inmunodeficiencia Adquirida
/
Inhibidores de la Proteasa del VIH
/
Apoptosis
/
Neutrófilos
Tipo de estudio:
Observational_studies
Límite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Apoptosis
Año:
2006
Tipo del documento:
Article
País de afiliación:
Italia