Zinc Is Required for FcεRI-Mediated Mast Cell Activation

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  • Koki Kabu
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology (RCAI) , Yokohama, Kanagawa ,
  • Satoru Yamasaki
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology (RCAI) , Yokohama, Kanagawa ,
  • Daisuke Kamimura
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology (RCAI) , Yokohama, Kanagawa ,
  • Yukitaka Ito
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology (RCAI) , Yokohama, Kanagawa ,
  • Aiko Hasegawa
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology (RCAI) , Yokohama, Kanagawa ,
  • Emi Sato
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology (RCAI) , Yokohama, Kanagawa ,
  • Hidemitsu Kitamura
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology (RCAI) , Yokohama, Kanagawa ,
  • Keigo Nishida
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology (RCAI) , Yokohama, Kanagawa ,
  • Toshio Hirano
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology (RCAI) , Yokohama, Kanagawa ,

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<jats:title>Abstract</jats:title> <jats:p>Zinc (Zn) is an essential nutrient, and its deficiency causes growth retardation, immunodeficiency, and neuronal degeneration. However, the precise roles and molecular mechanism(s) of Zn function in immune response have not been clarified. Mast cells (MCs) are granulated cells that play a pivotal role in allergic reactions and inflammation. The granules of MCs contain various chemical mediators and inflammatory cytokines that are released upon FcεRI cross-linking. In this study, we report that Zn is essential for MC activation both in vitro and in vivo. We showed that a Zn chelator, N,N,N,N-tetrakis (2-pyridylmethyl) ethylenediamine, inhibited in vivo allergic reactions such as PCA and PSA. Consistent with this, N,N,N,N-tetrakis (2-pyridylmethyl) ethylenediamine significantly inhibited the FcεRI-induced degranulation and cytokine production. We found that Zn was required for FcεRI-induced translocation of granules to the plasma membrane, a process that we have shown to be important for MC degranulation. In addition, we showed that Zn was essential for plasma membrane translocation of protein kinase C and subsequent nuclear translocation of NF-κB, leading to cytokine production, such as IL-6 and TNF-α. These results revealed that Zn was involved in multiple steps of FcεRI-induced MC activation and required for degranulation and cytokine production.</jats:p>

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