IgE-regulated loss, not IgE-regulated synthesis, controls expression of FcepsilonRI in human basophils.
IgE-regulated loss, not IgE-regulated synthesis, controls expression of FcepsilonRI in human basophils.
复制标题
IgE 调节的丢失，而不是 IgE 调节的合成，控制着人嗜碱性粒细胞中 FcepsilonRI 的表达。
作者：
D. MacGlashan;H. Xia;L. Schwartz;J. Gong
嗜碱性粒细胞和肥大细胞上高亲和力受体的表达受免疫球蛋白 E (IgE) 抗体调节。最近的研究表明，调节是通过 IgE 与受体本身的相互作用发生的，但这种控制的机制尚不清楚。我们采用理论和实验方法，研究了几种竞争模型，这些模型重点关注 IgE Fc 受体 (FcepsilonRI) 是否存在 IgE 调节的丢失、IgE 调节的合成或同时丢失和合成调节。我们报道，从占据的 FcepsilonRI 中去除 IgE 仅导致未占据的受体加速损失，而占据的受体没有损失，并且当所有受体都被占据时，总受体也没有损失。与之前的研究一起，这些结果证实存在 IgE 调节的受体损失。使用 (35)S-甲硫氨酸脉冲标记对 FcepsilonRIalpha 的合成速率进行检查表明，在存在或不存在 IgE 的情况下，合成速率没有差异。类似地，IgE 的存在或不存在对 FcepsilonRI 的 α、β 或 γ 亚基的 mRNA 水平没有影响。通过模型模拟，我们发现，根据起始 FcepsilonRI 密度与在不存在 IgE 的情况下培养 1 周后密度变化之间的关系，可以将调节合成模型与调节损失/恒定合成模型区分开来。此类研究的实验数据符合不包括合成调节的调节损失模型。综上所述，这些结果表明 IgE 仅通过调节受体从细胞表面丢失的速率来调节 FcepsilonRI 的细胞表面表达。
Expression of the high-affinity receptor on basophils and mast cells is modulated by immunoglobulin E (IgE) antibody. Recent studies have shown that modulation occurs through interaction of IgE with the receptor itself, but the mechanisms underlying this control are not understood. Taking both a theoretical and experimental approach, we examined several competing models that focus on whether there is IgE-regulated loss, IgE-regulated synthesis, or both regulated loss and synthesis of the Fc receptor for IgE (FcepsilonRI). We report that removing IgE from occupied FcepsilonRI resulted in an accelerated loss only in the unoccupied receptor, with no loss of occupied receptors and no loss of total receptors when all receptors were occupied. Together with previous studies, these results establish that there was IgE-regulated loss of receptors. An examination of synthetic rates of FcepsilonRIalpha using pulse-labeling with (35)S-methionine indicated no difference in synthetic rates in the presence or absence of IgE. Similarly, the presence or absence of IgE had no influence on the levels of mRNA for either alpha, beta, or gamma subunits of FcepsilonRI. Using model simulations, we found that regulated-synthesis models could be distinguished from regulated-loss/constant-synthesis models on the basis of the relationship between starting FcepsilonRI densities and changes in density after culture for 1 week in the absence of IgE. Experimental data from this type of study fit a regulated-loss model that did not include regulation of synthesis. Taken together, these results suggest that IgE regulates cell surface expression of FcepsilonRI only by regulating the rate that receptor is lost from the cell surface.