Role of zinc transporter in allergic reaction

Abstract

Zinc (Zn) is an essential nutrient and its deficiency causes growth retardation, immunodeficiency, and neuronal degeneration. Zn homeostasis is tightly controlled by transporting through Zn transporters and by buffering via metallothioneins, all of which are involved in the intricate regulation of Zn concentration and distribution in individual cells. Research in understanding of these molecules has progressed with application of genetic techniques, which allow us to clarify the diverse role of Zn in vivo and in vitro. However, the precise roles and molecular mechanism(s) of Zn's function in allergic response have not been clarified. Mast cells are granulated cells that play a pivotal role in allergic reactions. The granules of mast cells contain various chemical mediators and inflammatory cytokines that are released upon FcεRI crosslinking. In this article, I will describe a role of Zn/Zn transporter in FcεRI-mediated mast cell degranulation and cytokine production. Furthermore, Zn acts as an intracellular signaling molecule, that is, a molecule whose intracellular status is altered in response to an extracellular stimulus in mast cell, and that is capable of transducing the extracellular stimulus into an intracellular signaling event, like Ca2+. I have proposed that there are two classes of Zn signaling: "Early" and "Late" Zn signaling. In this review, I discussed how Zn and its homeostasis affect biological events especially for mast cell-mediated allergy response. © 2011 The Pharmaceutical Society of Japan.