Cobbina Samuel Jerry, Xu Hai, Zhao Ting, Mao Guanghua, Zhou Zhaoxiang, Wu Xueshan, Liu Hongyang, Zou Yanmin, Wu Xiangyang, Yang Liuqing
School of the Environment and Safety Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu, China.
School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, China.
Fish Shellfish Immunol. 2015 Dec;47(2):1032-42. doi: 10.1016/j.fsi.2015.11.003. Epub 2015 Nov 6.
Concerns over the potential health effects of mixtures of low concentration heavy metals on living organisms keep growing by the day. However, the toxicity of low concentration metal mixtures on the immune system of fish species has rarely been investigated. In this study, the zebrafish model was employed to investigate the effect on innate immune and antioxidant-related gene expressions, on exposure to environmentally relevant concentrations of individual and mixtures of Pb (0.01 mg/L), Hg (0.001 mg/L), As (0.01 mg/L) and Cd (0.005 mg/L). Messenger-RNA (mRNA) levels of IL1β, TNF-α, IFNγ, Mx, Lyz, C3B and CXCL-Clc which are closely associated with the innate immune system were affected after exposing zebrafish embryos to metals for 120 h post fertilization (hpf). Individual and mixtures of metals exhibited different potentials to modulate innate-immune gene transcription. IL1β genes were significantly up regulated on exposure to Pb + As (2.01-fold) and inhibited on exposure to Pb + Hg + Cd (0.13-fold). TNF-α was significantly inhibited on exposure to As (0.40-fold) and Pb + As (0.32-fold) compared to control. Metal mixtures generally up regulated IFNγ compared to individual metals. Additionally, antioxidant genes were affected, as CAT and GPx gene expressions generally increased, whiles Mn-SOD and Zn/Cu-SOD reduced. Multivariate analysis showed that exposure to individual metals greatly influenced modulation of innate immune genes; whiles metal mixtures influenced antioxidant gene expressions. This suggests that beside oxidative stress, there may be other pathways influencing gene expressions of innate immune and antioxidant-related genes. Low concentration heavy metals also affect expression of development-related (wnt8a and vegf) genes. Altogether, the results of this study clearly demonstrate that low concentration individual and mixtures of metals in aquatic systems will greatly influence the immune system. It is indicative that mechanisms associated with toxicity of metal mixtures is complex, however, further studies to elucidate them are ongoing in our research laboratory.
人们对低浓度重金属混合物对生物有机体潜在健康影响的担忧日益加剧。然而，低浓度金属混合物对鱼类免疫系统的毒性却鲜有研究。在本研究中，采用斑马鱼模型来研究暴露于环境相关浓度的铅（0.01毫克/升）、汞（0.001毫克/升）、砷（0.01毫克/升）和镉（0.005毫克/升）的单一金属及混合物时，对先天免疫和抗氧化相关基因表达的影响。在受精后120小时（hpf）将斑马鱼胚胎暴露于金属中后，与先天免疫系统密切相关的白细胞介素1β（IL1β）、肿瘤坏死因子-α（TNF-α）、干扰素γ（IFNγ）、Mx蛋白、溶菌酶（Lyz）、补体3B（C3B）和CXC趋化因子Clc的信使核糖核酸（mRNA）水平受到了影响。单一金属及金属混合物表现出不同的调节先天免疫基因转录的潜力。暴露于铅+砷时，IL1β基因显著上调（2.01倍），而暴露于铅+汞+镉时则受到抑制（0.13倍）。与对照组相比，暴露于砷（0.40倍）和铅+砷（0.32倍）时，TNF-α显著受到抑制。与单一金属相比，金属混合物通常会上调IFNγ。此外，抗氧化基因也受到影响，因为过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）基因表达通常增加，而锰超氧化物歧化酶（Mn-SOD）和锌/铜超氧化物歧化酶（Zn/Cu-SOD）则减少。多变量分析表明，暴露于单一金属对先天免疫基因的调节有很大影响；而金属混合物则影响抗氧化基因的表达。这表明除了氧化应激外，可能还有其他途径影响先天免疫和抗氧化相关基因的表达。低浓度重金属也会影响发育相关（wnt8a和vegf）基因的表达。总之，本研究结果清楚地表明，水生系统中低浓度的单一金属和金属混合物将极大地影响免疫系统。这表明与金属混合物毒性相关的机制很复杂，不过，我们的研究实验室正在进行进一步的研究以阐明这些机制。
