論文 - 詳細
| RRC ID | 72836 |
|---|---|
| 著者 | Nakashima-Kaneda K, Matsuda A, Mizuguchi H, Sasaki-Sakamoto T, Saito H, Ra C, Okayama Y. |
| タイトル | Regulation of IgE-dependent zinc release from human mast cells. |
| ジャーナル | Int Arch Allergy Immunol |
| Abstract |
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. |
| 巻・号 | 161 Suppl 2 |
| ページ | 44-51 |
| 公開日 | 2013-1-1 |
| DOI | 10.1159/000350359 |
| PII | 000350359 |
| PMID | 23711853 |
| MeSH | Cation Transport Proteins / genetics Cation Transport Proteins / immunology Cell Degranulation / genetics Cell Degranulation / immunology Cell Line Cells, Cultured Gene Expression Regulation Histamine Release Humans Immunoglobulin E / immunology* Mast Cells / immunology* Mast Cells / metabolism* RNA Interference Receptors, IgE / metabolism* Zinc / metabolism* |
| IF | 2.917 |
| リソース情報 | |
| 研究用ヒト臍帯血幹細胞 | |