Increased Fas-mediated apoptosis in polymorphonuclear cells from HIV-infected patients

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Date
2011-05-30Author
Palabras Clave
Apoptosis, ERK, Fas/ FasL, HIV, Neutrophils, Polymorphonuclear cellsMetadata
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Neutrophils represent an important line of innate host defence against invading microorganisms and
their functional detriment during HIV infection, including accelerated spontaneous cell death, has been
shown to contribute to AIDS development. Neutrophils are susceptible to apoptosis via Fas and an
interaction between Fas and FasL was suggested originally as a mechanism to explain constitutive neutrophil
apoptosis. We have explored some intracellular pathways leading to PMN apoptosis from 28
HIV-infected patients and 24 healthy volunteers. As previously reported, accelerated spontaneous apoptosis
was observed in HIV+ patients, but this did not correlate with viral load. Furthermore, an
increase in the level of spontaneous apoptosis was detected in neutrophils from HIV-infected patients
following inhibition of ERK, suggesting an impairment of this kinase pathway during the early stages
of infection which may contribute to PMN dysfunction. An elevated susceptibility to undergo apoptosis
was observed following cross-linking of Fas, which correlated both with viral load and co-expression of
Fas/FasL surface molecules. Different mechanisms for spontaneous and Fas-induced apoptosis are proposed which together contribute to the neutropenia and secondary infections observed during the progression
to AIDS.
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Información Adicional
Correo Electrónico | sihamsa@ula.ve gata@ula.ve, guillermondi@gmail.com lberruet@ula.ve |
Descripción | Blackwell Publishing Ltd, Clinical and Experimental Immunology, 137:166–172 |
Colación | 166–172 |