Amorphous silica nanoparticles (nSP50) exacerbate hepatic damage through the activation of acquired cell-mediated immunity
Amorphous silica nanoparticles (nSP50) exacerbate hepatic damage through the activation of acquired cell-mediated immunity
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无定形二氧化硅纳米颗粒 (nSP50) 通过激活获得性细胞介导的免疫而加剧肝损伤
DOI：
10.1088/2632-959x/ac4bb0
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发表时间：
2022
期刊：
影响因子：
3
通讯作者：
Tsutsumi Yasuo
中科院分区：
文献类型：
--
作者：
Eto Shun-ichi;Higashisaka Kazuma;Koshida Aoi;Sato Kenta;Ogura Mao;Sakurai Miyuki;Tsujino Hirofumi;Nagano Kazuya;Tsutsumi Yasuo
由于其创新功能，纳米粒子在各个行业的使用不断扩大。然而，一个关键问题是纳米颗粒是否会引起意想不到的生物效应。尽管许多研究都集中在先天免疫上，但关于纳米颗粒是否通过影响获得性免疫来诱导生物反应的信息很少。在这里，为了评估无定形二氧化硅纳米颗粒对获得性免疫的影响，我们分析了用无定形二氧化硅纳米颗粒（直径 50 nm；nSP50）预处理后急性毒性的变化。在免疫功能正常的小鼠中，用nSP50预处理在生化和病理学上加剧了nSP50诱导的肝损伤，而用nSP50预处理并没有加剧免疫缺陷小鼠的肝损伤。与此相一致的是，在用 nSP50 预处理的动物中，用抗 CD8 抗体消除 CD8+ 细胞，导致静脉内给药后肝损伤标志物（如 ALT 和 AST）的血浆水平低于用同种型匹配的对照抗体治疗的血浆水平。最后，无论使用何种刺激剂，对 nSP50 预处理的小鼠脾细胞的刺激都会促进 IFN-γ 的释放。此外，阻断 IFN-γ 降低了 nSP50 预处理小鼠的血浆 ALT 和 AST 水平。总的来说，这些数据表明，nSP50 诱导的获得性免疫通过激活细胞毒性 T 淋巴细胞导致肝损伤加剧。
Due to their innovative functions, the use of nanoparticles in various industries has been expanding. However, a key concern is whether nanoparticles induce unexpected biological effects. Although many studies have focused on innate immunity, information on whether nanoparticles induce biological responses through effects on acquired immunity is sparse. Here, to assess the effects of amorphous silica nanoparticles on acquired immunity, we analyzed changes in acute toxicities after pretreatment with amorphous silica nanoparticles (50 nm in diameter; nSP50). Pretreatment with nSP50 biochemically and pathologically exacerbated nSP50-induced hepatic damage in immunocompetent mice, while pretreatment with nSP50 did not exacerbate hepatic damage in immunodeficient mice. Consistent with this, the depletion of CD8+ cells with an anti-CD8 antibody in animals pretreated with nSP50 resulted in lower plasma levels of hepatic injury markers such as ALT and AST after an intravenous administration than treatment with an isotype-matched control antibody. Finally, stimulation of splenocytes promoted the release of IFN-γ in nSP50-pretreated mice regardless of the stimulator used. Moreover, the blockade of IFN-γ decreased plasma levels of ALT and AST levels in nSP50-pretreated mice. Collectively, these data show that nSP50-induced acquired immunity leads to exacerbation of hepatic damage through the activation of cytotoxic T lymphocytes.