2002 Fiscal Year Final Research Report Summary
Two faces of IgE-mediated reaction ; Analysis of IgE-dependent inhibitory response
| Project/Area Number |
13670448
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | the University of Tokyo |
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Principal Investigator |
YAMAGUCHI Masao The University of Tokyo, Department of Allergy and Rheumatology, Research Associate, 医学部附属病院, 助手 (10302704)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAI Koichi The University of Tokyo, Department of Bioregulatory Function, Associate Professor, 大学院・医学系研究科, 客員助教授 (10156630)
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| Project Period (FY) |
2001 – 2002
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| Keywords | allergy / basophils / mast cells / IgE / desensitization |
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| Research Abstract |
In this study, we investigated the various aspects of IgE-dependent events in basophils or mast cells, focusing on the cellular changes other than activation. We obtained the following findings ;
1. Relatively weak, by 30 to 50%, changes in surface FcεRI levels on basophils or mast cells were functionally important. Cultured mast cells with upregulated/down-regulated FcεRI levels showed enhanced/reduced degranulation in response to IgE-mediated stimulation, respectively. Glucocorticoids demonstrated down-regulation of surface FcεRI densities on cultured mouse mast cells, thereby affecting IgE-mediated degranulation.
2. Following treatment in physiological culture conditions, human basophils showed potent desensitization ; IgE-mediated near-threshold stimulation of basophils resulted in complete loss of degranulating capacity in response to later, maximal stimulation with either antigen or anti-IgE antibody. Importantly, basophils with enhanced levels of surface FcεRI expression demonstrated upregulated desensitization.
3. Surface expression of FcεRI on human eosinophils was inducible by IL-4 plus IgE, suggesting the similarities in regulatory mechanisms between mast cell and eosinophil surface FcεRI expression.
Through this series of study, it was strongly suggested that IgE and FcεRI-mediated cellular stimulation is affected by various mechanisms ; IgE itself augments, but glucocorticoids suppresses, IgE-mediated events through effects on surface FcεRI levels. Our results also suggest that IgE-dependent stimulation of human basophils induces not only activation but desensitization, which is also upregulated after IgE-dependent increase in surface IgE densities on basophils. Thus, IgE-dependent outcomes of basophils and mast cells may be regulated in a complex manner in both extracellular and intracellular levels.
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