Key Lab of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
Key Lab of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
J Hazard Mater. 2016 Nov 5;317:570-578. doi: 10.1016/j.jhazmat.2016.06.023. Epub 2016 Jun 13.
The toxicological risks of silver nanoparticles (AgNPs) have attracted widespread attention, and many studies have been published that have contributed to understanding AgNPs-induced toxicity. However, little attention has been paid to the low-dose effects of AgNPs and the related toxicological mechanism is still unclear. Here, we show that short-term exposure to AgNPs at low doses induces a substantial increase in human umbilical vein endothelial cells (HUVECs) monolayer permeability, whereas Ag ions at low doses do not induce an observable increase in monolayer permeability. This effect is independent of oxidative stress and apoptosis. Scanning electron microscopy confirms that AgNPs adhere to the cell membrane after 1h exposure. Furthermore, adhesion of AgNPs to the cell membrane can trigger vascular endothelial (VE)-cadherin phosphorylation at Y658 followed by VE-cadherin internalization, which lead to the increase in endothelial monolayer permeability. Our data show that surface interactions of AgNPs with the cell membrane, in other words, the particle effect, is a major factor leading to endothelial dysfunction following low-dose and short-term exposure. Our findings will contribute to understanding the health effects and the toxicological mechanisms of AgNPs.
银纳米粒子（AgNPs）的毒理学风险引起了广泛关注，许多研究已经发表，有助于了解 AgNPs 诱导的毒性。然而，人们对 AgNPs 的低剂量效应关注甚少，相关的毒理学机制仍不清楚。在这里，我们表明，AgNPs 在低剂量下的短期暴露会导致人脐静脉内皮细胞（HUVEC）单层通透性显著增加，而低剂量的 Ag 离子不会引起可见的单层通透性增加。这种效应不依赖于氧化应激和细胞凋亡。扫描电子显微镜证实，AgNPs 在暴露 1 小时后附着在细胞膜上。此外，AgNPs 与细胞膜的粘附可以触发血管内皮（VE）-钙粘蛋白在 Y658 处的磷酸化，随后 VE-钙粘蛋白内化，导致内皮单层通透性增加。我们的数据表明，AgNPs 与细胞膜的表面相互作用，换句话说，颗粒效应，是导致低剂量和短期暴露后内皮功能障碍的主要因素。我们的发现将有助于理解 AgNPs 的健康影响和毒理学机制。
