Two faces of IgE-mediated reaction ; Analysis of IgE-dependent inhibitory response

在这项研究中，我们研究了嗜碱性粒细胞或肥大细胞中IgE依赖事件的各个方面，重点是细胞的变化而不是激活。我们得到了以下发现：1.相对较弱的，30%到50%的嗜碱性粒细胞或肥大细胞表面FcεRI水平的变化在功能上是重要的。FcεRI表达上调/下调的肥大细胞对Ig E介导的刺激反应分别表现为脱颗粒增强和脱颗粒减少。结论1.糖皮质激素可下调培养的小鼠肥大细胞表面FcεRI密度，从而影响Ig E介导的脱粒。在生理培养条件下处理后，人嗜碱性粒细胞表现出强烈的脱敏作用；IgE介导的对嗜碱性粒细胞的近阈值刺激导致脱颗粒能力完全丧失，而后者是抗原或抗IgE抗体的最大刺激。重要的是，表面FcεRI表达水平升高的嗜碱性粒细胞表现出上调的脱敏作用。IL-4加免疫球蛋白E可诱导人嗜酸粒细胞表面表达FcεRI，提示肥大细胞和嗜酸性粒细胞表面FcεRI表达的调节机制相似。通过这一系列研究，强烈表明ε和FcεRI介导的细胞刺激受多种机制的影响；Ig E本身增强，但糖皮质激素抑制，Ig E介导的事件通过影响表面Fc Fc Ri水平而发挥作用。我们的结果还表明，依赖于IgE的人嗜碱性粒细胞的刺激不仅能诱导激活，而且还能诱导脱敏，这在依赖于IgE的嗜碱性细胞表面IgE密度增加后也会上调。因此，嗜碱性粒细胞和肥大细胞的IgE依赖的结果可能在细胞外和细胞内水平以一种复杂的方式受到调节。

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.