Laboratoire de recherche en inflammation et physiologie des granulocytes, Université du Québec, INRS-Institut Armand-Frappier, Laval, QC, Canada.
Toxicol In Vitro. 2010 Apr;24(3):1002-8. doi: 10.1016/j.tiv.2009.12.007. Epub 2009 Dec 21.
This paper describes the in vitro effects of titanium dioxide (TiO(2)) nanoparticles (NPs) upon human neutrophils. Kinetic experiments revealed no cell necrosis after 24h of treatment with TiO(2) (0-100 microg/ml). In contrast, TiO(2)-induced change in cellular morphology in a concentration-dependent manner in neutrophils over time, indicating its potential to activate these cells. To further support this, we demonstrated that TiO(2) markedly and rapidly induced tyrosine phosphorylation events, including phosphorylation of two key enzymes, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases-1/2 (Erk-1/2). We also determined the effects of TiO(2) on two neutrophil functions requiring a longer exposure period between NPs and cells: apoptosis and cytokine production. Interestingly, at concentrations >or=20 microg/ml, TiO(2) inhibited neutrophil apoptosis in a concentration-dependent manner after 24h of treatment. Supernatants from TiO(2)-induced neutrophils were harvested after 24h and tested for the presence of 36 different analytes (cytokines, chemokines) using an antibody array assay. TiO(2) treatment increased production of 13 (36%) analytes, including IL-8, which exhibited the greatest increase ( approximately 16 x control cell levels). The increased production of IL-8 was confirmed by ELISA. We conclude that TiO(2) exerts important neutrophil agonistic properties in vitro.
本文描述了二氧化钛（TiO2）纳米粒子（NPs）对人嗜中性粒细胞的体外影响。动力学实验表明，在 24 小时的 TiO2（0-100 微克/毫升）处理后，没有细胞坏死。相比之下，TiO2 以时间和浓度依赖的方式导致中性粒细胞的细胞形态发生变化，表明其具有激活这些细胞的潜力。为了进一步支持这一点，我们证明 TiO2 显著且快速地诱导酪氨酸磷酸化事件，包括两个关键酶的磷酸化，p38 丝裂原激活蛋白激酶（MAPK）和细胞外信号调节激酶-1/2（Erk-1/2）。我们还确定了 TiO2 对两种需要更长的 NP 和细胞暴露时间的中性粒细胞功能的影响：细胞凋亡和细胞因子产生。有趣的是，在浓度>或=20 微克/毫升时，TiO2 以浓度依赖的方式抑制中性粒细胞凋亡。处理 24 小时后，从 TiO2 诱导的中性粒细胞中收集上清液，并使用抗体阵列测定法检测 36 种不同分析物（细胞因子、趋化因子）的存在。TiO2 处理增加了 13（36%）种分析物的产生，包括 IL-8，其增加幅度最大（约为对照细胞水平的 16 倍）。ELISA 证实了 IL-8 产量的增加。我们得出结论，TiO2 在体外对中性粒细胞具有重要的激动作用。
