Translational Immunology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Toxicol Appl Pharmacol. 2012 Oct 1;264(1):94-103. doi: 10.1016/j.taap.2012.07.021. Epub 2012 Jul 27.
Metal oxide nanoparticles are widely used in the paint and coating industry as well as in cosmetics, but the knowledge of their possible interactions with the immune system is very limited. Our aims were to investigate if commercially available TiO(2) and ZnO nanoparticles may affect different human immune cells and their production of exosomes, nano-sized vesicles that have a role in cell to cell communication. We found that the TiO(2) or ZnO nanoparticles at concentrations from 1 to 100μg/mL did not affect the viability of primary human peripheral blood mononuclear cells (PBMC). In contrast, monocyte-derived dendritic cells (MDDC) reacted with a dose dependent increase in cell death and caspase activity to ZnO but not to TiO(2) nanoparticles. Non-toxic exposure, 10μg/mL, to TiO(2) and ZnO nanoparticles did not significantly alter the phenotype of MDDC. Interestingly, ZnO but not TiO(2) nanoparticles induced a down regulation of FcγRIII (CD16) expression on NK-cells in the PBMC population, suggesting that subtoxic concentrations of ZnO nanoparticles might have an effect on FcγR-mediated immune responses. The phenotype and size of exosomes produced by PBMC or MDDC exposed to the nanoparticles were similar to that of exosomes harvested from control cultures. TiO(2) or ZnO nanoparticles could not be detected within or associated to exosomes as analyzed with TEM. We conclude that TiO(2) and ZnO nanoparticles differently affect immune cells and that evaluations of nanoparticles should be performed even at subtoxic concentrations on different primary human immune cells when investigating potential effects on immune functions.
金属氧化物纳米粒子在涂料和涂料工业以及化妆品中被广泛应用，但人们对它们与免疫系统可能发生的相互作用知之甚少。我们的目的是研究市售的 TiO(2) 和 ZnO 纳米粒子是否会影响不同的人类免疫细胞及其外泌体的产生，外泌体是一种在细胞间通讯中起作用的纳米大小的囊泡。我们发现，TiO(2)或 ZnO 纳米粒子在 1 至 100μg/mL 的浓度下不会影响原代人外周血单核细胞（PBMC）的活力。相比之下，单核细胞衍生的树突状细胞（MDDC）对 ZnO 纳米粒子的反应是细胞死亡和半胱天冬酶活性的剂量依赖性增加，而对 TiO(2)纳米粒子则没有。非毒性暴露于 10μg/mL 的 TiO(2)和 ZnO 纳米粒子不会显著改变 MDDC 的表型。有趣的是，ZnO 纳米粒子而非 TiO(2)纳米粒子诱导 PBMC 中的 NK 细胞上 FcγRIII（CD16）表达下调，表明亚毒性浓度的 ZnO 纳米粒子可能对 FcγR 介导的免疫反应产生影响。暴露于纳米粒子的 PBMC 或 MDDC 产生的外泌体的表型和大小与对照培养物中收获的外泌体相似。TEM 分析未发现 TiO(2)或 ZnO 纳米粒子在纳米粒子内或与其相关联。我们得出结论，TiO(2)和 ZnO 纳米粒子对免疫细胞的影响不同，当研究对免疫功能的潜在影响时，即使在亚毒性浓度下，也应对不同的原代人类免疫细胞进行纳米粒子的评估。
