Torres Anaelle, Collin-Faure Véronique, Diemer Hélène, Moriscot Christine, Fenel Daphna, Gallet Benoît, Cianférani Sarah, Sergent Jacques-Aurélien, Rabilloud Thierry
Chemistry and Biology of Metals Laboratory, Université Grenoble Alpes, Centre National de la Recherche Scientifique, Commissariat à l'Energie Atomique, Interdisciplinary Research Institute of Grenoble, 38054 Grenoble, France.
Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), Centre National de la Rech erche Scientifique, Hubert Curien Pluridisciplinary Institute UMR 7178, Strasbourg University, 67087 Strasbourg, France.
Nanomaterials (Basel). 2022 Apr 22;12(9):1424. doi: 10.3390/nano12091424.
Synthetic amorphous silica (SAS) is a nanomaterial used in a wide variety of applications, including the use as a food additive. Two types of SAS are commonly employed as a powder additive, precipitated silica and fumed silica. Numerous studies have investigated the effects of synthetic amorphous silica on mammalian cells. However, most of them have used an exposure scheme based on a single dose of SAS. In this study, we have used instead a repeated 10-day exposure scheme in an effort to better simulate the occupational exposure encountered in daily life by consumers and workers. As a biological model, we have used the murine macrophage cell line J774A.1, as macrophages are very important innate immune cells in the response to particulate materials. In order to obtain a better appraisal of the macrophage responses to this repeated exposure to SAS, we have used proteomics as a wide-scale approach. Furthermore, some of the biological pathways detected as modulated by the exposure to SAS by the proteomic experiments have been validated through targeted experiments. Overall, proteomics showed that precipitated SAS induced a more important macrophage response than fumed SAS at equal dose. Nevertheless, validation experiments showed that most of the responses detected by proteomics are indeed adaptive, as the cellular homeostasis appeared to be maintained at the end of the exposure. For example, the intracellular glutathione levels or the mitochondrial transmembrane potential at the end of the 10 days exposure were similar for SAS-exposed cells and for unexposed cells. Similarly, no gross lysosomal damage was observed after repeated exposure to SAS. Nevertheless, important functions of macrophages such as phagocytosis, TNFα, and interleukin-6 secretion were up-modulated after exposure, as was the expression of important membrane proteins such as the scavenger receptors, MHC-II, or the MAC-1 receptor. These results suggest that repeated exposure to low doses of SAS slightly modulates the immune functions of macrophages, which may alter the homeostasis of the immune system.
合成无定形二氧化硅（SAS）是一种纳米材料，应用广泛，包括用作食品添加剂。两种类型的SAS通常用作粉末添加剂，即沉淀二氧化硅和气相二氧化硅。许多研究调查了合成无定形二氧化硅对哺乳动物细胞的影响。然而，其中大多数研究采用的是基于单剂量SAS的暴露方案。在本研究中，我们改用了为期10天的重复暴露方案，以便更好地模拟消费者和工人在日常生活中遇到的职业暴露情况。作为生物学模型，我们使用了小鼠巨噬细胞系J774A.1，因为巨噬细胞是对颗粒物质作出反应时非常重要的天然免疫细胞。为了更好地评估巨噬细胞对这种重复暴露于SAS的反应，我们采用蛋白质组学作为一种大规模方法。此外，蛋白质组学实验检测到的一些因暴露于SAS而被调节的生物学途径已通过靶向实验得到验证。总体而言，蛋白质组学表明，在同等剂量下，沉淀SAS比气相SAS诱导的巨噬细胞反应更强烈。然而，验证实验表明，蛋白质组学检测到的大多数反应确实是适应性的，因为在暴露结束时细胞内稳态似乎得以维持。例如，暴露10天后，暴露于SAS的细胞和未暴露细胞的细胞内谷胱甘肽水平或线粒体跨膜电位相似。同样，重复暴露于SAS后未观察到明显的溶酶体损伤。然而，暴露后巨噬细胞的重要功能如吞噬作用、TNFα和白细胞介素-6分泌上调，重要膜蛋白如清道夫受体、MHC-II或MAC-1受体的表达也上调。这些结果表明，重复暴露于低剂量的SAS会轻微调节巨噬细胞的免疫功能，这可能会改变免疫系统的稳态。
