Flagellin delays spontaneous human neutrophil apoptosis

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Neutrophils are short-lived cells that rapidly undergo apoptosis. However, their survival can be regulated by signals from the environment. Flagellin, the primary component of the bacterial flagella, is known to induce neutrophil activation. In this study we examined the ability of flagellin to modu...

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Autores principales: Salamone, Gabriela V., Petracca, Yanina, Fuxman Bass, Juan I., Rumbo, Martín, Nahmod, Karen A., Gabelloni, María L., Vermeulen, Mónica E., Matteo, Mario J., Geffner, Jorge R., Trevani, Aanalía S.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2010
Materias:
Ciencias Exactas
apoptosis
flagellin
neutrophil
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/82426
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-82426
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
apoptosis
flagellin
neutrophil
spellingShingle Ciencias Exactas
apoptosis
flagellin
neutrophil
Salamone, Gabriela V.
Petracca, Yanina
Fuxman Bass, Juan I.
Rumbo, Martín
Nahmod, Karen A.
Gabelloni, María L.
Vermeulen, Mónica E.
Matteo, Mario J.
Geffner, Jorge R.
Trevani, Aanalía S.
Flagellin delays spontaneous human neutrophil apoptosis
topic_facet Ciencias Exactas
apoptosis
flagellin
neutrophil
description Neutrophils are short-lived cells that rapidly undergo apoptosis. However, their survival can be regulated by signals from the environment. Flagellin, the primary component of the bacterial flagella, is known to induce neutrophil activation. In this study we examined the ability of flagellin to modulate neutrophil apoptosis. Neutrophils cultured for 12 and 24 h in the presence of flagellin from Salmonella thyphimurim at concentrations found in pathological situations underwent a marked prevention of apoptosis. In contrast, Helicobacter pylori flagellin did not affect neutrophil survival, suggesting that Salmonella flagellin exerts the antiapoptotic effect by interacting with TLR5. The delaying in apoptosis mediated by Salmonella flagellin was coupled to higher expression levels of the antiapoptotic protein Mcl-1 and lower levels of activated caspase-3. Analysis of the signaling pathways indicated that Salmonella flagellin induced the activation of the p38 and ERK1/2 MAPK pathways as well as the PI3K/Akt pathway. Furthermore, it also stimulated IBα degradation and the phosphorylation of the p65 subunit, suggesting that Salmonella flagellin also triggers NF-B activation. Moreover, the pharmacological inhibition of ERK1/2 pathway and NF-B activation partially prevented the antiapoptotic effects exerted by flagellin. Finally, the apoptotic delaying effect exerted by flagellin was also evidenced when neutrophils were cultured with whole heat-killed S. thyphimurim. Both a wild-type and an aflagellate mutant S. thyphimurim strain promoted neutrophil survival; however, when cultured in low bacteria/neutrophil ratios, the flagellate bacteria showed a higher capacity to inhibit neutrophil apoptosis, although both strains showed a similar ability to induce neutrophil activation. Taken together, our results indicate that flagellin delays neutrophil apoptosis by a mechanism partially dependent on the activation of ERK1/2 MAPK and NF-B. The ability of flagellin to delay neutrophil apoptosis could contribute to perpetuate the inflammation during infections with flagellated bacteria.
format Articulo
Articulo
author Salamone, Gabriela V.
Petracca, Yanina
Fuxman Bass, Juan I.
Rumbo, Martín
Nahmod, Karen A.
Gabelloni, María L.
Vermeulen, Mónica E.
Matteo, Mario J.
Geffner, Jorge R.
Trevani, Aanalía S.
author_facet Salamone, Gabriela V.
Petracca, Yanina
Fuxman Bass, Juan I.
Rumbo, Martín
Nahmod, Karen A.
Gabelloni, María L.
Vermeulen, Mónica E.
Matteo, Mario J.
Geffner, Jorge R.
Trevani, Aanalía S.
author_sort Salamone, Gabriela V.
title Flagellin delays spontaneous human neutrophil apoptosis
title_short Flagellin delays spontaneous human neutrophil apoptosis
title_full Flagellin delays spontaneous human neutrophil apoptosis
title_fullStr Flagellin delays spontaneous human neutrophil apoptosis
title_full_unstemmed Flagellin delays spontaneous human neutrophil apoptosis
title_sort flagellin delays spontaneous human neutrophil apoptosis
publishDate 2010
url http://sedici.unlp.edu.ar/handle/10915/82426
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