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Differential immunotoxic effects of inorganic and organic mercury species in vitro.

机译:无机和有机汞物种在体外的差异免疫毒性作用。

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Despite the fact that humans are exposed to multiple forms of mercury (elemental, inorganic, and organic), most research on mercury toxicity has focused on methylmercury (MeHg) and on neurotoxic outcomes and mechanisms. Recent work has indicated that the immunotoxic effects of mercury compounds may be significant contributors to human disease as well as mechanistically relevant to other target organ toxicities. In this study, we compared the effects of inorganic Hg (iHg) to organic Hg species (MeHg and ethylmercury, EtHg) in human peripheral blood mononuclear cells (PBMCs) in vitro at sub-cytotoxic concentrations, using methods developed to characterize response of human PBMCs to iHg in vitro. PBMCs were isolated from six volunteer blood donors (three males and three females) and cultured in the presence and absence of lipopolysaccharide (LPS) and low levels (up to 200nM of each Hg species, separately) for 24h in culture. Cell culture supernatants were analyzed for cytokine concentrations with a bead-based multiplex assay. We report that iHg and MeHg both increase pro-inflammatory cytokine release in LPS-stimulated PBMCs, while EtHg decreases IFN-gamma release as well pro-inflammatory cytokine release. IL-17 release is significantly increased only in response to iHg treatment. Levels of anti-inflammatory cytokines (IL-1Ra and IL-10) were not significantly altered by any Hg treatment. These results indicate that both organic and inorganic species of Hg can affect the human immune system, but that they may exert different effects on immune function.
机译:尽管人类暴露于多种形式的汞(元素,无机和有机汞),但有关汞毒性的大多数研究都集中在甲基汞(MeHg)以及神经毒性结果和机制上。最近的工作表明,汞化合物的免疫毒性作用可能是导致人类疾病的重要因素,并且与其他靶器官毒性在机理上也有关系。在这项研究中,我们采用了表征人类反应特性的方法,在亚细胞毒性浓度下比较了人体外周血单个核细胞(PBMC)中无机汞(iHg)与有机汞物种(MeHg和乙基汞,EtHg)的影响PBMC体外转化为iHg。从六名自愿献血者(三名男性和三名女性)中分离出PBMC,并在存在和不存在脂多糖(LPS)和低水平(每种Hg种类分别高达200nM)的条件下培养24小时。细胞培养上清液中基于珠的多重测定分析细胞因子浓度。我们报告说,iHg和MeHg都增加LPS刺激的PBMC中促炎细胞因子的释放,而EtHg降低IFN-γ释放以及促炎细胞因子的释放。仅响应iHg处理,IL-17的释放才显着增加。任何汞治疗均未显着改变抗炎细胞因子(IL-1Ra和IL-10)的水平。这些结果表明,汞的有机物和无机物均可影响人体的免疫系统,但它们可能对免疫功能产生不同的影响。

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