Silver nanoparticles promote procoagulant activity of red blood cells: a potential risk of thrombosis in susceptible population
Silver nanoparticles promote procoagulant activity of red blood cells: a potential risk of thrombosis in susceptible population
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DOI：
10.1186/s12989-019-0292-6
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发表时间：
2019-02-14
影响因子：
10
通讯作者：
Chung, Jin-Ho
中科院分区：
文献类型：
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作者：
Bian, Yiying;Kim, Keunyoung;Chung, Jin-Ho
纳米银（AgNP）因其独特的抗菌、抗病毒和抗癌活性而广泛应用于医疗实践。然而，随着 AgNP 使用的增加，对其潜在毒性的担忧也在升级。在此，我们证明了 AgNP 的潜在血栓形成作用是由红细胞 (RBC) 的促凝血活性介导的。在新鲜分离的人 RBC 中，AgNP（而非银微粒 (AgMP)）引起形态变化、磷脂酰丝氨酸 (PS) 暴露和微泡 (MV) 生成，这是红细胞中促凝血活性的关键指标，浓度范围（ae 100 μg/mL）为均无明显溶血。与此相符的是，AgNP 增强了凝血酶的生成以及红细胞与内皮细胞的粘附，而 AgMP 则不然。研究发现氧化应激、细胞内钙增加和 ATP 消耗是 AgNP 促凝血作用的基础，从而导致膜氨基磷脂转位酶活性改变。这些体外研究结果在大鼠体内得到了很好的重现，静脉内暴露于 AgNP 显着促进了静脉血栓形成。值得注意的是，从癌症患者体内分离出的红细胞本身就具有血栓形成的风险，因此对 AgNP 的促凝血作用更加敏感。此外，AgNP 显着增强了化疗药物紫杉醇的促凝血作用。总的来说，这些结果表明 AgNP 可能通过促进红细胞的促凝血活性而具有促血栓风险，因此在癌症患者等对血栓形成敏感的人群中使用时应谨慎。
Silver nanoparticles (AgNP) are widely used in medical practices owing to their distinct antibacterial, antiviral and anticancer activities. However, with increasing use of AgNP, concerns over its potential toxicity are also escalating. Here, we demonstrated the potential thrombotic effect of AgNP which was mediated by the procoagulant activity of red blood cells (RBCs).In freshly isolated human RBCs, AgNP, but not silver microparticles (AgMP), elicited morphological changes, phosphatidylserine (PS) exposure and microvesicles (MV) generation, the key indicators of procoagulant activity in RBCs at concentration ranges (ae 100 mu g/mL) that were free of significant hemolysis. In line with this, AgNP potentiated thrombin generation and adherence of RBCs to endothelial cells, while AgMP did not. Oxidative stress, intracellular calcium increase and ATP depletion were found to underlie the procoagulant effects of AgNP, which led to altered activity of membrane aminophospholipid translocases. These in vitro findings were well reproduced in rat in vivo, where intravenously exposure to AgNP promoted venous thrombosis significantly. Of note, RBCs isolated from cancer patients, who inherently convey the risk of thrombogenesis, were more sensitive to the procoagulant effects of AgNP. In addition, AgNP significantly potentiated the procoagulant effects of a chemotherapeutic drug, paclitaxel.Collectively, these results suggest that AgNP may have prothrombotic risks by promoting procoagulant activity of RBCs and caution shall be taken for its use in the population sensitive to thrombosis like cancer patients.