Interleukin-5 priming of human eosinophils alters Siglec-8-mediated apoptosis pathways

Esra Nutku-Bilir, Sherry A. Hudson, Bruce S. Bochner

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Previously, we have identified the sequential activation of reactive oxygen species (ROS), mitochondria, and caspase-3, -8, and -9, in Siglec-8-mediated eosinophil apoptosis. Cytokine priming, which normally prolongs eosinophil survival, paradoxically potentiated this proapoptotic effect. The mechanisms of Siglec-8-mediated apoptosis after priming were therefore explored. Using IL-5 as the priming stimulus, the rate of Siglec-8-induced eosinophil apoptosis was found to be enhanced compared with unprimed cells, and mechanisms differed after IL-5 priming in that neither a pan-caspase inhibitor, nor a specific caspase-3 inhibitor, could override apoptosis. IL-5 priming also accelerated Siglec-8-mediated dissipation of mitochondrial membrane potential. Finally, both the mitochondrial electron transport inhibitor rotenone, and the ROS inhibitors diphenyleneiodonium and antimycin, completely inhibited Siglec-8-mediated apoptosis, even after IL-5 priming. These data demonstrate that IL-5 priming enhances Siglec-8-mediated mitochondrial and ROS-dependent eosinophil apoptosis and eliminates caspase dependence. The potential clinical implication of these findings is that cytokine priming, as often occurs in vivo in asthma and other hypereosinophilic disorders, may render eosinophils from such patients especially susceptible to the proapoptotic effects of a Siglec-8-engaging therapeutic agent.

Original languageEnglish (US)
Pages (from-to)121-124
Number of pages4
JournalAmerican journal of respiratory cell and molecular biology
Issue number1
StatePublished - Jan 2008
Externally publishedYes


  • Apoptosis
  • Caspases
  • Eosinophils
  • Mitochondria
  • Siglec-8

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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