Silica-based nanoparticle uptake and cellular response by primary microglia.
Silica-based nanoparticle uptake and cellular response by primary microglia.
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DOI：
10.1289/ehp.0901534
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发表时间：
2010-05
影响因子：
10.4
通讯作者：
Guilarte TR
中科院分区：
文献类型：
--
作者：
Choi J;Zheng Q;Katz HE;Guilarte TR
二氧化硅纳米颗粒（SiNPs）正在被配制用于细胞成像和中枢神经系统（CNS）中的非病毒基因递送，但目前还不清楚SiNPs一旦进入CNS会引起什么潜在影响。作为CNS的常驻巨噬细胞，小胶质细胞是最有可能对SiNP进入大脑做出反应的细胞。一旦激活，它们能够经历形态和功能变化。我们使用原代大鼠小胶质细胞研究了SiNP暴露的影响。我们使用透射电子显微镜和荧光共聚焦显微镜观察小胶质细胞对SiNPs的摄取。在不同浓度的SiNP暴露后，测量小胶质细胞的功能，包括吞噬作用、活性氧（ROS）和活性氮（RNS）的产生、促炎基因的表达和细胞因子的释放。小胶质细胞能够在所有测试浓度下贪婪地摄取SiNP。这些相同的浓度没有引起细胞毒性或吞噬活性的变化。SiNPs确实增加了细胞内ROS和RNS的产生。我们还观察到在所有测试浓度下肿瘤坏死因子-α基因表达显著降低，并且在SiNP的最高浓度下考克斯-2（环氧合酶-2）基因表达显著增加。细胞因子释放分析显示可检测水平的白细胞介素-1 β。这是第一项证明SiNP在原代小胶质细胞中的体外作用的研究。我们的研究结果表明，非常低水平的SiNPs能够改变小胶质细胞的功能。增加的ROS和RNS产生，促炎基因的变化和细胞因子释放不仅可能对小胶质细胞功能产生不利影响，而且还影响周围的神经元。
Silica nanoparticles (SiNPs) are being formulated for cellular imaging and for nonviral gene delivery in the central nervous system (CNS), but it is unclear what potential effects SiNPs can elicit once they enter the CNS. As the resident macrophages of the CNS, microglia are the cells most likely to respond to SiNP entry into the brain. Upon activation, they are capable of undergoing morphological and functional changes. We examined the effects of SiNP exposure using primary rat microglia. We observed microglial uptake of SiNPs using transmission electron and fluorescence confocal microscopy. Microglial functions, including phagocytosis, generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), expression of proinflammatory genes, and cytokine release, were measured after SiNP exposure at different concentrations. Microglia are capable of avidly taking up SiNPs at all concentrations tested. These same concentrations did not elicit cytotoxicity or a change in phagocytic activity. SiNPs did increase the productions of both intracellular ROS and RNS. We also observed a significant decrease in tumor necrosis factor-α gene expression at all concentrations tested and a significant increase in COX-2 (cyclooxygenase-2) gene expression at the highest concentration of SiNPs. Analysis of cytokine release showed a detectable level of interleukin-1β. This is the first study demonstrating the in vitro effects of SiNPs in primary microglia. Our findings suggest that very low levels of SiNPs are capable of altering microglial function. Increased ROS and RNS production, changes in proinflammatory genes, and cytokine release may not only adversely affect microglial function but also affect surrounding neurons.
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影响因子：
10.4
作者：
Long TC;Tajuba J;Sama P;Saleh N;Swartz C;Parker J;Hester S;Lowry GV;Veronesi B
通讯作者：
Veronesi B
表面修饰二氧化硅纳米粒子的生物分布和尿液排泄的体内研究
影响因子：
7.4
作者：
He, Xiaoxiao;Nie, Hailong;Zhang, Pengfei
通讯作者：
Zhang, Pengfei
影响因子：
4.5
作者：
Lockman, PR;Koziara, JM;Allen, DD
通讯作者：
Allen, DD
影响因子：
3.8
作者：
Lin, Weisheng;Huang, Yue-wern;Ma, Yinfa
通讯作者：
Ma, Yinfa
影响因子：
13.3
作者：
Napierska, Dorota;Thomassen, Leen C. J.;Hoet, Peter H.
通讯作者：
Hoet, Peter H.