Mast cell desensitization inhibits calcium flux and aberrantly remodels actin.
Mast cell desensitization inhibits calcium flux and aberrantly remodels actin.
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DOI：
10.1172/jci87492
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发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Abraham SN
中科院分区：
文献类型：
--
作者：
Ang WX;Church AM;Kulis M;Choi HW;Burks AW;Abraham SN
快速脱敏（DS）是一种广泛使用和有效的快速抑制ige介导的过敏反应的临床策略。然而，这一过程背后的细胞靶点和潜在机制尚不清楚。最近的研究表明肥大细胞（MCs）是退行性椎体滑移的主要靶细胞。在这里，我们建立了一个小鼠被动过敏反应模型，证实与MCs有关，并进行了体外实验来评估DS对MCs的影响。与之前的报道相反，我们确定脱敏的MCs在DS后的细胞表面仍然存在功能性IgE。尽管脱敏后MCs脱粒明显减少，但高亲和的IgE受体FcεRI仍然能够在脱敏的MCs中传导信号。此外，我们发现肌动蛋白细胞骨架的位移及其与fc - ri的持续关联阻碍了脱敏的MCs激发钙反应的能力，而钙反应对MCs脱颗粒至关重要。总之，这些发现表明脱敏的MCs中脱颗粒反应的减少是由异常的肌动蛋白重塑引起的，这可能有助于改善DS治疗过敏反应的方法。
Rush desensitization (DS) is a widely used and effective clinical strategy for the rapid inhibition of IgE-mediated anaphylactic responses. However, the cellular targets and underlying mechanisms behind this process remain unclear. Recent studies have implicated mast cells (MCs) as the primary target cells for DS. Here, we developed a murine model of passive anaphylaxis with demonstrated MC involvement and an in vitro assay to evaluate the effect of DS on MCs. In contrast with previous reports, we determined that functional IgE remains on the cell surface of desensitized MCs following DS. Despite notable reductions in MC degranulation following DS, the high-affinity IgE receptor FcεRI was still capable of transducing signals in desensitized MCs. Additionally, we found that displacement of the actin cytoskeleton and its continued association with FcεRI impede the capacity of desensitized MCs to evoke the calcium response that is essential for MC degranulation. Together, these findings suggest that reduced degranulation responses in desensitized MCs arise from aberrant actin remodeling, providing insights that may lead to improvement of DS treatments for anaphylactic responses.