Exposure of single-walled carbon nanotubes impairs the functions of primarily cultured murine peritoneal macrophages
Exposure of single-walled carbon nanotubes impairs the functions of primarily cultured murine peritoneal macrophages
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单壁碳纳米管的暴露会损害原代培养的小鼠腹膜巨噬细胞的功能
DOI：
10.3109/17435390.2012.694487
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发表时间：
2013-08-01
期刊：
影响因子：
5
通讯作者：
Zhao, Lixia
中科院分区：
文献类型：
--
作者：
Dong, Ping-Xuan;Wan, Bin;Zhao, Lixia
摘要随着单壁碳纳米管（SWCNTs）在生物医学领域的研究和应用日益广泛，了解其免疫反应变得越来越重要。巨噬细胞和T细胞在清除外来物质和病原体以及调节免疫反应中起重要作用。在这项工作中，利用原代培养的小鼠腹腔巨噬细胞和纯化的脾T细胞来确定单壁碳纳米管和酸官能化单壁碳纳米管（AF-SWCNT）对免疫系统，特别是对巨噬细胞功能的毒性作用。将巨噬细胞暴露于0-50 μg/ml CNT 24 h，通过活/死和annexin-V-FITC/PI分析未发现显著的细胞毒性。透射电镜观察表明，AF-SWCNTs主要通过吞噬作用被吞噬，并定位于巨噬细胞的溶酶体中。线粒体膜电位和蛋白酶体亚单位基因表达的测量表明，10和50 μg/ml的AF-SWCNTs可以浓度依赖性方式损害线粒体功能和蛋白酶体形成。功能分析表明，20 μg/ml的碳纳米管对巨噬细胞吞噬率有显著影响，5 μg/ml的AF-SWCNTs对乳胶珠的吞噬率有抑制作用。AF-SWCNTs和SWCNTs分别在10 μ g/ml和50 μg/ml浓度下影响辅助细胞功能。此外，AF-SWCNT通过诱导IFN-γ和TNF的产生使幼稚T细胞偏向于Th 1型分化，这意味着AF-SWCNT暴露时存在Th 1相关疾病（例如自身免疫性疾病和炎症）的潜在风险。
Abstract It is increasingly important to understand the single-walled carbon nanotubes' (SWCNTs) immune response as their increasingly biomedical researches and applications. Macrophages and T cells play important roles in scavenging foreign materials and pathogens and regulating immune response. In this work, primarily cultured murine peritoneal macrophages and purified splenic T cells were utilised to determine the toxic effects of SWCNTs and acid-functionalised SWCNTs (AF-SWCNTs) on the immune system, especially on macrophage functions. Macrophages were exposed to 0–50 μg/ml of CNTs for 24 h and no significant cytotoxicity was found by live/dead and annexin-V-FITC/PI analyses. The TEM images revealed that AF-SWCNTs were engulfed mostly through phagocytosis and located in lysosomes of macrophages. Measurement of mitochondrial membrane potential and proteasome subunit gene expression demonstrated that 10 and 50 μg/ml AF-SWCNTs could damage mitochondrial function and proteasome formation in a concentration-dependent manner. Functional analyses revealed that the percentage of phagocytic cells were affected significantly by 20 μg/ml CNTs, and 5 μg/ml AF-SWCNTs inhibited the phagocytic efficiency of latex beads in macrophages. The accessory cell function was affected by both AF-SWCNTs and SWCNTs at concentrations of 10 and 50 μg/ml, respectively. Furthermore, AF-SWCNT biased naïve T-cell differentiation to Th1 type by inducing the production of IFN-γ and TNF, implying the potential risk of Th1-associated diseases (e.g. autoimmune diseases and inflammation) on AF-SWCNT exposure.