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Lactoferrin inhibits neutrophil apoptosis via blockade of proximal apoptotic signaling events.
Francis, Nigel; Wong, See Heng; Hampson, Peter; Wang, Keqing; Young, Stephen P; Deigner, Hans Peter; Salmon, Michael; Scheel-Toellner, Dagmar; Lord, Janet M.
Afiliación
  • Francis N; MRC Centre for Immune Regulation, Institute of Biomedical Research, Birmingham University, Birmingham B15 2TT, UK.
Biochim Biophys Acta ; 1813(10): 1822-6, 2011 Oct.
Article en En | MEDLINE | ID: mdl-21781990
ABSTRACT
Neutrophils are the most abundant leukocyte and have a short lifespan, dying by apoptosis approximately five days after leaving the bone marrow. Their apoptosis can be delayed at sites of inflammation to extend their functional lifespan, but inappropriate inhibition of apoptosis contributes to chronic inflammatory disease. Levels of the physiological iron chelator lactoferrin are raised at sites of inflammation and we have shown previously that iron-unsaturated lactoferrin inhibited human neutrophil apoptosis, but the mechanisms involved were not determined. Here we report that the anti-apoptotic effect of lactoferrin is dependent upon its iron saturation status as iron-saturated lactoferrin did not affect neutrophil apoptosis. We also show that the effect of lactoferrin is mediated at an early stage in apoptosis as it inhibited activation of sphingomyelinase, generation of ceramide, activation of caspase 8 and Bax and cleavage of Bid. Lactoferrin did not inhibit apoptosis induced by exogenous ceramide, supporting the proposal that it acts upstream of ceramide generation. We therefore conclude that raised lactoferrin levels are likely to contribute to chronic inflammation by delaying neutrophil apoptosis and that this is achieved by inhibiting proximal apoptotic signaling events.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Apoptosis / Lactoferrina / Neutrófilos Límite: Humans Idioma: En Revista: Biochim Biophys Acta Año: 2011 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Apoptosis / Lactoferrina / Neutrófilos Límite: Humans Idioma: En Revista: Biochim Biophys Acta Año: 2011 Tipo del documento: Article País de afiliación: Reino Unido