The in vitro immune modulation by cadmium depends on the way of cell activation
The in vitro immune modulation by cadmium depends on the way of cell activation
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DOI：
10.1016/j.tox.2006.01.026
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发表时间：
2006-05-01
期刊：
影响因子：
4.5
通讯作者：
Lehmann, Irina
中科院分区：
文献类型：
--
作者：
Hemdan, Nasr Y. A.;Emmrich, Frank;Lehmann, Irina
在以其毒性和全球分布而闻名的环境污染物中，重金属是最令人担忧的。虽然镉的毒理学已经得到了广泛的研究，但关于低剂量镉暴露所引起的免疫调节的信息却很少。我们的目的是在两种激活模型中评估人类免疫活性细胞短期暴露于生物相关剂量的低剂量镉所引起的免疫调节效应。用细菌抗原(热灭活肠炎沙门氏菌)或单抗(单抗：抗CD3/抗CD28/抗CD40)激活人外周血单个核细胞，用四甲基偶氮唑盐比色法检测细胞活力，用ELISA法检测细胞因子释放，用实时荧光定量RT-PCR检测细胞因子基因表达。结果表明，除了已知的镉毒性效应外，0.013~13.3mU/M的剂量对细胞因子的产生也有不同的影响。在mAb激活的情况下，与IL-4和IL-10的产生相比，低剂量Cd对IL-1β、肿瘤坏死因子(TNF)-α和干扰素(干扰素)-γ的分泌有很大的抑制作用。这表明了一种偏向于2型的免疫反应。在细菌抗原刺激下，IL-10的释放较干扰素-γ和肿瘤坏死因子-α受到高度抑制，IL-4检测不到。这些结果表明，低剂量的镉具有免疫调节作用，这种调节的方向取决于细胞激活的途径。总体而言，在通过T细胞受体刺激的细胞中，CD使对2型的免疫反应两极化。然而，细菌抗原诱导的极化的1型反应不能被CD的影响所压倒。(C)2006爱思唯尔爱尔兰有限公司。保留所有权利。
Among environmental contaminants known for their toxicity and worldwide distribution, heavy metals are of primary concern. Although the toxicology of cadmium (Cd) has been extensively studied, little information is available on the immunomodulation driven by exposure to low doses of Cd. We aimed to evaluate the immunomodulatory effects elicited by short-term exposure of human immunocompetent cells to low biologically relevant doses of Cd in two activation models. Human peripheral blood mononuclear cells, activated either by bacterial antigens (heat-killed Salmonella Enteritidis) or monoclonal antibodies (mAb: anti-CD3/anti-CD28/anti-CD40), were exposed to Cd acetate for 24 h. Cell vitality was determined by MTT assay, cytokine release by ELISA, and cytokine gene expression by real-time RT-PCR. The results demonstrated that, in addition to the known toxic effects of Cd, doses from 0.013 to 13.3 mu M exert differential effects on cytokine production. In the case of mAb-activation, secretion of interleukin (IL)-1 beta, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma was greatly inhibited at low Cd doses compared to production of IL-4 and IL-10. This indicates a type-2-biased immune response. Under stimulation by bacterial antigens, release of IL-10 was highly suppressed compared to that of IFN-gamma and TNF-alpha; IL-4 was undetectable. These results imply that low Cd doses exert immunomodulatory effects and the direction of this modulation depends on the pathway to cell activation. Overall, Cd polarizes the immune response toward type-2 in cells stimulated via T cell receptors. However, a polarized type-1 response induced by bacterial antigens could not be overwhelmed by the effects of Cd. (c) 2006 Elsevier Ireland Ltd. All rights reserved.