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The Journal of Immunology, 2006, 177: 1296-1305.
Copyright © 2006 by The American Association of Immunologists

Zinc Is Required for Fc{epsilon}RI-Mediated Mast Cell Activation1

Koki Kabu*,{dagger}, Satoru Yamasaki*, Daisuke Kamimura*, Yukitaka Ito*,{dagger}, Aiko Hasegawa*,{dagger}, Emi Sato*,{dagger}, Hidemitsu Kitamura*, Keigo Nishida* and Toshio Hirano2,*,{dagger}

* Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology (RCAI), Yokohama, Kanagawa, Japan; and {dagger} Laboratories of Developmental Immunology, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka, Japan

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 Fc{epsilon}RI 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 Fc{epsilon}RI-induced degranulation and cytokine production. We found that Zn was required for Fc{epsilon}RI-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-{kappa}B, leading to cytokine production, such as IL-6 and TNF-{alpha}. These results revealed that Zn was involved in multiple steps of Fc{epsilon}RI-induced MC activation and required for degranulation and cytokine production.




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