Direct effects of airborne PM2.5 exposure on macrophage polarizations
Direct effects of airborne PM2.5 exposure on macrophage polarizations
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空气中 PM2.5 暴露对巨噬细胞极化的直接影响
DOI：
10.1016/j.bbagen.2016.03.033
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发表时间：
2016-12-01
影响因子：
3
通讯作者：
Ding, Wenjun
中科院分区：
文献类型：
--
作者：
Zhao, Qingjie;Chen, Hui;Ding, Wenjun
背景技术背景：空气动力学直径小于2.5微米的大气颗粒物（PM2.5）的暴露在流行病学上与疾病有关。空气污染物对先天免疫的潜在影响引起了人们的关注。巨噬细胞作为机体的第一道防线，能够诱导炎症反应。然而，是否PM2.5暴露影响巨噬细胞polarizations.METHODS：我们使用新鲜分离的巨噬细胞作为一个模型系统，以证明PM2.5对巨噬细胞极化的影响仍不清楚。采用实时荧光定量PCR和流式细胞术检测细胞因子和关键分子标志物的表达。结果：PM2.5可增加促炎细胞因子粒细胞-巨噬细胞集落刺激因子（GM-CSF）、白细胞介素-6（IL-6）、白细胞介素-1 β（IL-1 β）、肿瘤坏死因子α（TNF α）的表达。PM2.5还增强了脂多糖（LPS）诱导的M1极化，即使没有证据表明细胞活力的变化。然而，PM2.5以剂量依赖的方式显著减少线粒体的数量。用活性氧（ROS）清除剂NAC预处理，阻止了ROS的增加，挽救了PM2.5影响的M1反应，但不能挽救M2反应。结论：PM2.5暴露通过ROS途径显著增强炎性M1极化，而PM2.5暴露通过mTOR依赖性途径抑制抗炎性M2极化。目前的研究表明，短期暴露于PM2.5会影响炎症M1和抗炎M2巨噬细胞极化的平衡，这可能与空气污染引起的免疫紊乱和疾病有关。(C)2016爱思唯尔B. V.保留所有权利。
BACKGROUND: Exposure of atmospheric particulate matter with an aerodynamic diameter less than 2.5 mu m (PM2.5) is epidemiologically associated with illnesses. Potential effects of air pollutants on innate immunity have raised concerns. As the first defense line, macrophages are able to induce inflammatory response. However, whether PM2.5 exposure affects macrophage polarizations remains unclear.METHODS: We used freshly isolated macrophages as a model system to demonstrate effects of PM2.5 on macrophage polarizations. The expressions of cytokines and key molecular markers were detected by real-time PCR, and flow cytometry. The specific inhibitors and gene deletion technologies were used to address the molecular mechanisms.RESULTS: PM2.5 increased the expression of pro-inflammatory cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha). PM2.5 also enhanced the lipopolysaccharide (LPS)-induced M1 polarization even though there was no evidence in the change of cell viability. However, PM2.5 significantly decreased the number of mitochondria in a dose dependent manner. Pre-treatment with NAC, a scavenger of reactive oxygen species (ROS), prevented the increase of ROS and rescued the PM2.5-impacted M1 but not M2 response. However, mTOR deletion partially rescued the effects of PM2.5 to reduce M2 polarization.CONCLUSIONS: PM2.5 exposure significantly enhanced inflammatory M1 polarization through ROS pathway, whereas PM2.5 exposure inhibited anti-inflammatory M2 polarization through mTOR-dependent pathway.GENERAL SIGNIFICANCE: The present studies suggested that short-term exposure of PM2.5 acts on the balance of inflammatory M1 and anti-inflammatory M2 macrophage polarizations, which may be involved in air pollution-induced immune disorders and diseases. (C) 2016 Elsevier B.V. All rights reserved.