Immunoglobulin (Ig)E-mediated activation of mast cells has long been thought to occur only when FcϵRI receptor-bound IgE is cross-linked via multivalent antigens. However, recent studies have raised the possibility that mast cells may be activated by the binding of IgE to the FcϵRI receptor in the absence of antigen. Here we demonstrate that IgE binding without antigen induces the expression of histidine decarboxylase (HDC) in mouse interleukin (IL)-3–dependent bone marrow–derived mast cells (BMMCs). The induction of HDC by the binding of IgE was found to require an influx of extracellular calcium ions, which was attenuated by pretreatment with U73122, a phospholipase C inhibitor. Furthermore, the increase in HDC activity upon sensitization with IgE was completely suppressed by pretreatment of BMMCs with protein kinase C inhibitors, such as H7, staurosporine, and Gö6976. In addition, immediate activation of the tyrosine kinase Lyn was not detectable upon treatment with IgE. These results suggest that the binding of IgE to its receptor in the absence of antigen results in de novo synthesis of HDC in BMMCs through a signaling pathway distinct to that operating during antigen-stimulated FcϵRI activation.
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15 July 2002
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July 15 2002
Antigen-independent Induction of Histamine Synthesis by Immunoglobulin E in Mouse Bone Marrow–derived Mast Cells
Satoshi Tanaka,
Satoshi Tanaka
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
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Yuhji Takasu,
Yuhji Takasu
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
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Sonoko Mikura,
Sonoko Mikura
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
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Norio Satoh,
Norio Satoh
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
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Atsushi Ichikawa
Atsushi Ichikawa
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
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Satoshi Tanaka
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
Yuhji Takasu
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
Sonoko Mikura
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
Norio Satoh
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
Atsushi Ichikawa
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
Address correspondence to Atsushi Ichikawa, Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Phone: 81-75-753-4527; Fax: 81-75-753-4557; E-mail: [email protected]
*
Abbreviations used in this paper: BMMC, IL-3-dependent bone marrow–derived mast cell; HDC, l-histidine decarboxylase; MEK, MAPK/ERK kinase; PI3-kinase, phosphoinositide 3-kinase; PLC, phospholipase C; PKC, protein kinase C; TPA, 12-O-tetradecanoyl phorbol 13-acetate.
Received:
December 07 2001
Revision Received:
May 20 2002
Accepted:
June 13 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 196 (2): 229–235.
Article history
Received:
December 07 2001
Revision Received:
May 20 2002
Accepted:
June 13 2002
Citation
Satoshi Tanaka, Yuhji Takasu, Sonoko Mikura, Norio Satoh, Atsushi Ichikawa; Antigen-independent Induction of Histamine Synthesis by Immunoglobulin E in Mouse Bone Marrow–derived Mast Cells . J Exp Med 15 July 2002; 196 (2): 229–235. doi: https://doi.org/10.1084/jem.20012037
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