| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
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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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