Internalization of Libby amphibole asbestos and induction of oxidative stress in murine macrophages
Internalization of Libby amphibole asbestos and induction of oxidative stress in murine macrophages
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DOI：
10.1093/toxsci/kfm166
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发表时间：
2007-09-01
影响因子：
3.8
通讯作者：
Pfau, Jean C.
中科院分区：
文献类型：
--
作者：
Blake, David J.;Bolin, Celeste M.;Pfau, Jean C.
蒙大拿州利比的社区成员经历了严重的石棉接触，并因社区附近的石棉污染蛭石矿而患上了许多与石棉有关的疾病，包括纤维化和肺癌。石棉在受污染的蛭石中的形式已被表征为闪石族纤维。然而，这些纤维的致病作用以前没有被表征。本研究的目的是确定利比角闪石暴露在巨噬细胞的细胞后果相比，另一个良好的特点角闪石纤维;青石棉。我们的研究结果表明，利比石棉纤维内化的巨噬细胞和本地化的细胞质和细胞质空泡类似的青石棉纤维。Libby石棉纤维内化产生细胞内活性氧（ROS）的显着增加，由二氯荧光素二乙酸酯和二氢乙啶荧光测定，表明超氧阴离子是Libby石棉产生的ROS的主要贡献。暴露于利比石棉的巨噬细胞中超氧化物水平升高与总超氧化物歧化酶活性的显着抑制相一致。利比和青石棉都通过降低细胞内谷胱甘肽水平在暴露的巨噬细胞中产生氧化应激。有趣的是，青石棉，而不是利比石棉，在巨噬细胞中诱导显著的DNA损伤。这项研究提供的证据表明，利比和青石棉之间观察到的DNA损伤水平的差异可能是每种纤维的不同化学成分以及石棉暴露期间单独细胞通路的激活的综合结果。
The community members of Libby, MT, have experienced significant asbestos exposure and developed numerous asbestosrelated diseases including fibrosis and lung cancer due to an asbestos-contaminated vermiculite mine near the community. The form of asbestos in the contaminated vermiculite has been characterized in the amphibole family of fibers. However, the pathogenic effects of these fibers have not been previously characterized. The purpose of this study is to determine the cellular consequences of Libby amphibole exposure in macrophages compared to another well-characterized amphibole fiber; crocidolite asbestos. Our results indicate that Libby asbestos fibers are internalized by macrophages and localize to the cytoplasm and cytoplasmic vacuoles similar to crocidolite fibers. Libby asbestos fiber internalization generates a significant increase in intracellular reactive oxygen species (ROS) as determined by dichlorofluorescein diacetate and dihydroethidine fluorescence indicating that the superoxide anion is the major contributing ROS generated by Libby asbestos. Elevated superoxide levels in macrophages exposed to Libby asbestos coincide with a significant suppression of total superoxide dismutase activity. Both Libby and crocidolite asbestos generate oxidative stress in exposed macrophages by decreasing intracellular glutathione levels. Interestingly crocidolite asbestos, but not Libby asbestos, induces significant DNA damage in macrophages. This study provides evidence that the difference in the level of DNA damage observed between Libby and crocidolite asbestos may be a combined consequence of the distinct chemical compositions of each fiber as well as the activation of separate cellular pathways during asbestos exposure.