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

• DOI: 10.1073/pnas.1735525100
• Publication Date: 2003-10-29T06:26:18Z
• Authors: 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
• Keywords: Mice, Knockout; 0301 basic medicine; Leukotrienes; Hybridomas; Cell Survival; Receptors, IgE; Bone Marrow Cells; Mice, Inbred Strains; Immunoglobulin E; Flow Cytometry; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Genes, Reporter; Animals; Cytokines; Female; Interleukin-3; Mast Cells; Luciferases; Cells, Cultured; Histamine

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.