Zinc Is Required for FcεRI-Mediated Mast Cell Activation

Abstract

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.

Gab2, via PI-3K, Regulates ARF1 in FcεRI-Mediated Granule Translocation and Mast Cell Degranulation

“…Evidence for this pathway in mast cells was independently reported by other investigators (16)(17)(18). We further reported that zinc is required for FcεRI-induced granule translocation to the plasma membrane and mast cell degranulation (19,20).…”

“…We previously showed that zinc is involved in FcεRI-mediated granule translocation (19). To further characterize the zincdependent granule-translocation mechanism(s), we developed a screen for zinc-associated molecules in mast cells.…”

“…Confocal microscopy was carried out using the TCS SL system (Leica). The frequency of Ag-induced mast cell granule translocation was determined as described previously (11,19). At least 90 independent GFP + cells were counted for each experiment.…”

Cortisol stimulates the zinc signaling pathway and expression of metallothioneins and ZnT1 in rainbow trout gill epithelial cells

“…The mechanisms of glucocorticoid action have been attributed to gene expression of antiinflammatory genes such as annexin-1, IL-10, and inhibitors of the inflammatory transcription factor NF-B (25). These are cellular systems that are known to be modified by zinc (13,24,26,42). Thus it will be of interest to verify whether our observation that cortisol increases zinc influx in gill epithelial cells also occurs in other cell types, such as the lung.…”

Zinc Signals Are Essential for Lipopolysaccharide-Induced Signal Transduction in Monocytes

“…Recent reports indicate that zinc is required for the production of C-C chemokines from airway epithelium cells (2) and the activation of mast cells via FcRIs (3)(4)(5). In contrast, stimulation of dendritic cells with LPS (3), a component of the cell wall of Gram-negative bacteria, affects expression of the zinc transporters ZIP-6 and ZIP-10 and ZnT-1, ZnT-4, and ZnT-6; an event that is required for the LPS-induced increase in MHC class II surface expression (6).…”