Minimal requirements for IgE-mediated regulation of surface FcεRI
Minimal requirements for IgE-mediated regulation of surface FcεRI
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DOI：
10.4049/jimmunol.167.3.1290
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发表时间：
2001-08-01
影响因子：
4.4
通讯作者：
Kinet, JP
中科院分区：
文献类型：
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作者：
Borkowski, TA;Jouvin, MH;Kinet, JP
IgE-Fc epsilon RI网络在变态反应性炎症中起核心作用。免疫球蛋白E水平控制细胞表面Fc epsilon RI水平，反过来，Fc epsilon RI水平调节效应器反应的强度。用抗IgE抗体治疗过敏患者可诱导嗜碱性粒细胞上Fc epsilon RI表达减少，并减少由Ag触发的组胺释放。然而，IgE介导的Fc epsilon RI表达的调节机制仍不清楚。在这里，我们设计了一个体外模型系统，以建立由IgE调节Fc epsilon RI的最低细胞需求。使用这个系统，我们证明了转录调控、造血特异性因子和信号转导不是IgE介导的Fc epsilon RI表达增加所必需的。Ige与α链的结合是诱导Fc epsilon RI上调的最低要求。上调的速度与表达的基线水平无关。这种上调的机制是三个因素共同作用的结果：1)受体在细胞表面的稳定，防止受体内化和降解；2)使用预先形成的受体池，包括循环和最近合成的受体；以及3)持续的基础蛋白质合成水平。在体内，可能有其他因素参与调节这里所述的基本调控机制。
The IgE-Fc epsilon RI network plays a central role in allergic inflammation. IgE levels control cell surface levels of Fc epsilon RI and, in turn, Fc epsilon RI levels modulate the intensity of effector responses. Treatment of allergic patients with anti-IgE Abs has been shown to induce a decrease in Fc epsilon RI expression on basophils and a decrease in Ag-triggered histamine release. However, the mechanisms underlying IgE-mediated regulation of Fc epsilon RI expression remain unclear. Here, we designed an in vitro model system to establish the minimal cellular requirements for regulation of Fc epsilon RI by IgE. Using this system, we demonstrate that transcriptional regulation, hemopoietic-specific factors, and signaling are not required for IgE-mediated increases in Fc epsilon RI expression. IgE binding to the alpha -chain is the minimal requirement for the induction of Fc epsilon RI up-regulation. The rate of up-regulation is independent of the baseline level of expression. The mechanism of this up-regulation is the result of a combination of three factors: 1) stabilization of the receptor at the cell surface, which prevents receptor internalization and degradation; 2) use of a preformed pool of receptor comprising recycled and recently synthesized receptors; and 3) continued basal level of protein synthesis. It is possible that in vivo additional factors contribute to modulate the basic regulatory mechanism described here.