Regulation of IgE-Dependent Zinc Release from Human Mast Cells

• Published in: International archives of allergy and immunology Vol. 161; no. Suppl 2; pp. 44 - 51
• Main Authors: Nakashima-Kaneda, Kazuko, Matsuda, Akira, Mizuguchi, Hiroyuki, Sasaki-Sakamoto, Tomomi, Saito, Hirohisa, Ra, Chisei, Okayama, Yoshimichi
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2013
• Subjects: Allergies; Cation Transport Proteins - genetics; Cation Transport Proteins - immunology; Cell Degranulation - genetics; Cell Degranulation - immunology; Cell Line; Cells, Cultured; Cellular biology; Gene Expression Regulation; Histamine Release; Humans; Immunoglobulin E - immunology; Immunoglobulins; Mast Cells - immunology; Mast Cells - metabolism; Original Paper; Receptors, IgE - metabolism; RNA Interference; Zinc; Zinc - metabolism; Immunoglobulin E; Zinc; Human mast cell
• ISBN: 9783318024173; 3318024171
• ISSN: 1018-2438; 1423-0097
• DOI: 10.1159/000350359

Background: Zinc (Zn) affects many aspects of immune function, including thymic development and the activities of immune cells. Zn is also involved in many steps of high-affinity IgE receptor (FcεRI)-induced mast cell (MC) activation, which is required for degranulation and cytokine production. Intracellular Zn levels increase in mouse MCs after FcεRI stimulation. We previously reported that Zn distribution in a human MC line, LAD2, changed dramatically following FcεRI aggregation with synchrotron radiation microbeams. However, the kinetics of Zn distribution and the underlying mechanisms following FcεRI cross-linking remain unknown. Methods: We used cord-blood-derived MCs and LAD2 cells. Degranulation was assessed by β-hexosaminidase (β-hex) release. Extracellular Zn levels were determined by inductively coupled plasma atomic emission spectrometry or based on the fluorescence intensity of a Zn indicator. We also used RNAi to knockdown ZnT1 expression. mRNA expression levels were determined by real-time RT-PCR. Results: Zn was rapidly released from human MCs after FcεRI aggregation. The kinetics and optimal conditions for FcεRI cross-linking for Zn release were different from those for degranulation. Treating LAD2 cells with an intracellular Ca 2+ chelator significantly inhibited IgE-mediated β-hex release but not Zn release. We investigated IgE-mediated β-hex and Zn release with specific inhibitors of signaling pathways. Zn and β-hex release were partly correlated with but also partly independent of IgE. Knockdown of the Zn efflux transporter, ZnT1, significantly inhibited Zn release from human MCs. Conclusions: Our results indicate that IgE-dependent Zn release from human MCs involves signaling cascades that are distinct from those of degranulation. Thus, Zn may have a unique function as a mediator of allergic inflammation.