Fine particulate matter (PM2.5) enhances FcεRI-mediated signaling and mast cell function
Fine particulate matter (PM2.5) enhances FcεRI-mediated signaling and mast cell function
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细颗粒物 (PM2.5) 增强 FcγRI 介导的信号传导和肥大细胞功能。
DOI：
10.1016/j.cellsig.2019.01.010
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发表时间：
2019-05-01
影响因子：
4.8
通讯作者：
Zhang, Weiguo
中科院分区：
文献类型：
--
作者：
Jin, Yuefei;Zhu, Minghua;Zhang, Weiguo
持续暴露在环境中的细颗粒物(PM2.5)会加剧人类的过敏性疾病。肥大细胞在皮肤、粘膜、肺等周围组织的变态反应性炎症中起重要作用。高亲和力Fc受体的结合导致肥大细胞脱颗粒，释放各种高活性的介质，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激活和功能在很大程度上尚不清楚。为了研究PM2.5对肥大细胞的影响，我们使用骨髓来源的肥大细胞(BMMCs)来检测PM2.5是否影响Fc epsilon RI介导的信号转导、细胞因子的产生和脱颗粒。暴露于高剂量PM2.5可引起BMMCs明显的细胞凋亡和死亡。相比之下，暴露于低剂量PM2.5可促进肥大细胞脱颗粒和Fc epsilon RI介导的细胞因子产生。进一步的分析表明，PM2.5处理增加了Syk的激活，随后其底物包括LAT、PLC-Gamma 1和SLP-76的磷酸化。此外，PM2.5处理导致了PI3K和MAPK通路的激活。有趣的是，PM2.5的水溶部分被发现负责促进Fc epsilon RI介导的信号传递、肥大细胞脱颗粒和细胞因子的产生。我们的数据表明，PM2.5，主要是PM2.5的水溶性部分，可能通过增强Fc epsilon RI介导的信号转导而影响肥大细胞的激活。
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 Fc epsilon RI-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 Fc epsilon RI-mediated cytokine production. Further analysis showed that PM2.5 treatment increased Syk activation and subsequently phosphorylation of its substrates including LAT, PLC-gamma 1, 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 Fc epsilon RI-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 Fc epsilon RI-mediated signaling.