Exposure of RBL-2H3 Mast Cells to Ag⁺ Induces Cell Degranulation and Mediator Release

Authors: Suzuki Y.¹; Yoshimaru T.¹; Yamashita K.^{1, 2}; Matsui T.^{1, 2}; Yamaki M.²; Shimizu K.¹

Source: Biochemical and Biophysical Research Communications, Volume 283, Number 3, May 2001 , pp. 707-714(8)

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Abstract:

There is a growing need to understand the impact of environmental sulfhydryl group-reactive heavy metals on the immune system. Here we show that Ag⁺ induces mast cell degranulation, as does the aggregation of the high affinity immunoglobulin E receptor (Fc epsi RI). Micromolar quantities of Ag⁺ specifically induced degranulation of mast cell model rat basophilic leukemia (RBL-2H3) cells without showing cytotoxicity. The Ag⁺-mediated degranulation could be observed as rapidly as 5 min after the addition of the ions. Ag⁺ also induced a rapid change in tyrosine phosphorylation of multiple cellular proteins including the focal adhesion kinase but not Syk kinase. The Syk-selective inhibitor piceatannol and the Src family-selective tyrosine kinase inhibitor PP1 dose-dependently inhibited Fc epsi RI-mediated degranulation, whereas neither compound inhibited the Ag⁺-mediated degranulation. Furthermore, likewise Fc epsi RI aggregation, Ag⁺ also induced leukotriene secretion. These results show that Ag⁺ activates RBL-2H3 mast cells through a tyrosine phosphorylation-linked mechanism, which is distinct from that involved in Fc epsi RI-mediated activation. Copyright 2001 Academic Press.

Keywords: RBL-2H3 cells; silver ions; cell degranulation; leukotriene secretion; tyrosine phosphorylation

Language: English

Document Type: Research article

Affiliations: 1: Department of Immunology and Microbiology, Nihon University School of Medicine, Tokyo, 173-8610, Japan 2: Pharmaceutical Research Laboratory, Hitachi Chemical Company, Ltd., Ibaraki, 317-8555, Japan

Publication date: 2001-05-01