Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcεRI

Jiro Kitaura, Jinming Song, Mindy Tsai, Koichi Asai, Mari Maeda-Yamamoto, Attila Mocsai, Yuko Kawakami, Fu-Tong Liu, Clifford A. Lowell, B. George Barisas, Stephen J. Galli, Toshiaki Kawakami

Research output: Contribution to journalArticle

218 Scopus citations

Abstract

We demonstrate that binding of different IgE molecules (IgEs) to their receptor, FcεRI, induces a spectrum of activation events in the absence of a specific antigen and provide evidence that such activation reflects aggregation of FcεRI. Highly cytokinergic IgEs can efficiently induce production of cytokines and render mast cells resistant to apoptosis in an autocrine fashion, whereas poorly cytokinergic IgEs induce these effects inefficiently. Highly cytokinergic IgEs seem to induce more extensive FcεRI aggregation than do poorly cytokinergic IgEs, which leads to stronger mast cell activation and survival effects. These effects of both types of IgEs require Syk tyrosine kinase and can be inhibited by FcεRI disaggregation with monovalent hapten. In hybridoma-transplanted mice, mucosal mast cell numbers correlate with serum IgE levels. Therefore, survival effects of IgE could contribute to the pathogenesis of allergic disease.

Original languageEnglish (US)
Pages (from-to)12911-12916
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number22
DOIs
StatePublished - Oct 28 2003

ASJC Scopus subject areas

  • Genetics
  • General

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    Kitaura, J., Song, J., Tsai, M., Asai, K., Maeda-Yamamoto, M., Mocsai, A., Kawakami, Y., Liu, F-T., Lowell, C. A., Barisas, B. G., Galli, S. J., & Kawakami, T. (2003). Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcεRI. Proceedings of the National Academy of Sciences of the United States of America, 100(22), 12911-12916. https://doi.org/10.1073/pnas.1735525100