State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-environmental Sciences, The Chinese Academy of Science , Beijing , China.
Nanotoxicology. 2013 Aug;7(5):1028-42. doi: 10.3109/17435390.2012.694487. Epub 2012 Jun 14.
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.
了解单壁碳纳米管(SWCNTs)的免疫反应变得越来越重要,因为它们在生物医学研究和应用中的应用越来越广泛。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方面发挥着重要作用。在这项工作中,主要培养了鼠腹腔巨噬细胞和纯化的脾 T 细胞,以确定 SWCNTs 和酸功能化 SWCNTs(AF-SWCNTs)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 0-50μg/ml 的 CNTs 中 24 小时,通过死活和 Annexin-V-FITC/PI 分析未发现明显的细胞毒性。TEM 图像显示,AF-SWCNTs 主要通过吞噬作用被吞噬,并位于巨噬细胞的溶酶体中。线粒体膜电位和蛋白酶体亚基基因表达的测量表明,10 和 50μg/ml 的 AF-SWCNTs 可以以浓度依赖的方式损害线粒体功能和蛋白酶体形成。功能分析表明,20μg/ml CNTs 显著影响吞噬细胞的百分比,而 5μg/ml AF-SWCNTs 抑制了巨噬细胞中乳胶珠的吞噬效率。辅助细胞功能分别受到 10μg/ml 和 50μg/ml 的 AF-SWCNTs 和 SWCNTs 的影响。此外,AF-SWCNT 通过诱导 IFN-γ和 TNF 的产生,使幼稚 T 细胞偏向 Th1 型分化,这意味着在接触 AF-SWCNT 时存在与 Th1 相关疾病(例如自身免疫性疾病和炎症)相关的潜在风险。