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Tamoxifen augments the innate immune function of neutrophils through modulation of intracellular ceramide

Author

Listed:
  • Ross Corriden

    (University of California, San Diego
    University of California, San Diego)

  • Andrew Hollands

    (University of California, San Diego)

  • Joshua Olson

    (University of California, San Diego)

  • Jaclyn Derieux

    (University of California, San Diego
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego)

  • Justine Lopez

    (University of California, San Diego)

  • John T. Chang

    (University of California, San Diego)

  • David J. Gonzalez

    (University of California, San Diego
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego)

  • Victor Nizet

    (University of California, San Diego
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego
    Rady Children’s Hospital)

Abstract

Tamoxifen is a selective oestrogen receptor modulator widely used for the treatment of breast cancer. In addition to its activity as an oestrogen receptor agonist/antagonist, tamoxifen also modulates sphingolipid biosynthesis, which has been shown to play an important role in the regulation of neutrophil activity. Here, we find that tamoxifen stimulation enhances several pro-inflammatory pathways in human neutrophils, including chemotaxis, phagocytosis and neutrophil extracellular trap (NET) formation. The enhancement of NET production occurs via a ceramide/PKCζ-mediated pathway, and treatment with synthetic ceramide is sufficient to promote NET formation. Pretreatment of human neutrophils with tamoxifen boosts neutrophil bactericidal capacity against a variety of pathogens in vitro and enhances clearance of the leading human pathogen methicillin-resistant Staphylococcus aureus in vivo. Our results suggest that tamoxifen, and the lipid signalling pathways it modulates, merit further exploration as targets for boosting host innate immune function.

Suggested Citation

  • Ross Corriden & Andrew Hollands & Joshua Olson & Jaclyn Derieux & Justine Lopez & John T. Chang & David J. Gonzalez & Victor Nizet, 2015. "Tamoxifen augments the innate immune function of neutrophils through modulation of intracellular ceramide," Nature Communications, Nature, vol. 6(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9369
    DOI: 10.1038/ncomms9369
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