Persistent exposure to ambient fine particulate matter (PM2.5) can exacerbate allergic diseases in humans. Mast cells play an important role in allergic inflammation in peripheral tissues, such as skin, mucosa, and lung. Engagement of the high-affinity Fc receptor leads to mast cell degranulation, releasing a variety of highly active mediators including histamine, leukotrienes, and inflammatory cytokines. How PM2.5 exposure affects mast cell activation and function remains largely unknown. To characterize the effect of PM2.5 on mast cells, we used bone marrow-derived mast cells (BMMCs) to examine whether PM2.5 affected FcεRI-mediated signaling, cytokine production, and degranulation. Exposure to high doses of PM2.5 caused pronounced apoptosis and death of BMMCs. In contrast, exposure to low doses of PM2.5 enhanced mast cell degranulation and FcεRI-mediated cytokine production. Further analysis showed that PM2.5 treatment increased Syk activation and subsequently phosphorylation of its substrates including LAT, PLC-γ1, and SLP-76. Moreover, PM2.5 treatment led to activation of the PI3K and MAPK pathways. Intriguingly, water-soluble fraction of PM2.5 were found responsible for the enhancement of FcεRI-mediated signaling, mast cell degranulation, and cytokine production. Our data suggest that PM2.5, mainly water-soluble fraction of PM2.5, could affect mast cell activation through enhancing FcεRI-mediated signaling.

中文翻译：

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细颗粒物（PM2.5）增强FcεRI介导的信号传导和肥大细胞功能。

长期暴露于环境细颗粒物（PM2.5）会加剧人类的过敏性疾病。肥大细胞在皮肤，粘膜和肺等周围组织的变应性炎症中起重要作用。高亲和力Fc受体的参与导致肥大细胞脱粒，释放出各种高活性介质，包括组胺，白三烯和炎性细胞因子。PM2.5暴露如何影响肥大细胞的活化和功能仍然未知。为了表征PM2.5对肥大细胞的作用，我们使用了骨髓衍生的肥大细胞（BMMC）来检查PM2.5是否影响FcεRI介导的信号传导，细胞因子产生和脱颗粒。暴露于高剂量的PM2.5中会引起BMMC明显的凋亡和死亡。相反，暴露于低剂量的PM2中。5增强肥大细胞脱粒和FcεRI介导的细胞因子产生。进一步的分析表明，PM2.5处理可提高Syk活化并随后磷酸化其底物（包括LAT，PLC-γ1和SLP-76）。此外，PM2.5处理导致PI3K和MAPK途径的激活。有趣的是，发现PM2.5的水溶性部分负责FcεRI介导的信号传导，肥大细胞脱粒和细胞因子产生。我们的数据表明PM2.5（主要是PM2.5的水溶性部分）可以通过增强FcεRI介导的信号传导来影响肥大细胞激活。5种治疗导致PI3K和MAPK途径的激活。有趣的是，发现PM2.5的水溶性部分负责FcεRI介导的信号传导，肥大细胞脱粒和细胞因子产生。我们的数据表明，PM2.5（主要是PM2.5的水溶性部分）可以通过增强FcεRI介导的信号传导来影响肥大细胞激活。5种治疗导致PI3K和MAPK途径的激活。有趣的是，发现PM2.5的水溶性部分负责FcεRI介导的信号传导，肥大细胞脱粒和细胞因子产生。我们的数据表明，PM2.5（主要是PM2.5的水溶性部分）可以通过增强FcεRI介导的信号传导来影响肥大细胞激活。