Silver nanoparticle immunomodulatory potential in absence of direct cytotoxicity in RAW 264.7 macrophages and MPRO 2.1 neutrophils
Silver nanoparticle immunomodulatory potential in absence of direct cytotoxicity in RAW 264.7 macrophages and MPRO 2.1 neutrophils
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DOI：
10.1080/1547691x.2019.1588928
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Brown, Jared M.
中科院分区：
文献类型：
--
作者：
Alsaleh, Nasser B.;Minarchick, Valerie C.;Brown, Jared M.
工程纳米材料(ENM)正被广泛用于消费品和药品；因此，人类暴露的风险和潜在的不良后果越来越大。免疫系统在宿主防御和抵御环境因素的保护中至关重要，通常由包括巨噬细胞和中性粒细胞在内的先天效应免疫细胞启动和执行。以前的文献报道，免疫系统是ENM毒性的主要靶点；然而，关于ENM的免疫毒性，存在着不一致的观点。这可能是由于ENM的物理化学性质、所研究的细胞模型、生物冠形成等方面的差异。因此，本研究检测了消费和医疗产品中使用最多的ENM之一的银纳米颗粒(AgNP)在两个关键的天然免疫细胞模型中的毒性和免疫调节作用，例如RAW 264.7细胞(巨噬细胞)和分化的MPRO2.1细胞(早幼粒细胞/中性粒细胞)。结果表明，尽管产生了一系列的活性氧物种，但暴露在20 nm柠檬酸盐包被的AgNP中与主要的氧化损伤、炎症反应和细胞毒性无关。然而，最重要的是，预先暴露于AgNP 24小时，可以增强RAW 264.7细胞的吞噬能力，以及对内毒素的反应释放炎性细胞因子IL-6。在MPRO 2.1细胞中，AgNP预暴露也导致吞噬能力增强；然而，这些细胞对佛波酯(PMA)的反应表现出细胞脱颗粒(弹性酶释放)和氧化爆发的减少。综上所述，这些发现向我们表明，暴露于AgNP，尽管对这些细胞没有直接(细胞)毒性，但有可能改变免疫细胞的反应。这些发现强调了评估暴露于ENM后的免疫细胞功能的重要性，超出了标准终点，如氧化应激和细胞毒性。此外，这些发现进一步说明了了解ENM-细胞相互作用的潜在分子机制的重要性，特别是在免疫系统中。
Engineered nanomaterials (ENM) are being used in a wide range of consumer products and pharmaceuticals; hence, there is an increasing risk for human exposure and potential adverse outcomes. The immune system, vital in host defense and protection against environmental agents, is typically initiated and executed by innate effector immune cells including macrophages and neutrophils. Previous literature has reported the immune system as a major target of ENM toxicity; however, there is inconsistency regarding the immunotoxicity of ENM. This could be attributed to differences in ENM physicochemical properties, cellular models examined, biocorona formation, etc. Thus, the current study examined the toxicity and immunomodulatory effects of silver nanoparticles (AgNP), one of the most utilized ENM in consumer and medical products, in two key innate immune cell models, e.g. RAW 264.7 cells (macrophages) and differentiated MPRO 2.1 cells (promyelocytes/neutrophils). The results showed that despite a generation of reactive oxygen species, exposure to 20 nm citrate-coated AgNP was not associated with major oxidative damage, inflammatory responses, nor cytotoxicity. Nevertheless, and most importantly, pre-exposure to the AgNP for 24 h enhanced RAW 264.7 cell phagocytic ability as well as the release of inflammatory cytokine interleukin-6 in response to lipopolysaccharide (LPS). In MPRO 2.1 cells, AgNP pre-exposure also resulted in enhanced phagocytic ability; however, these cells manifest reduced cell degranulation (elastase release) and oxidative burst in response to phorbol myristate acetate (PMA). Taken together, these findings indicated to us that exposure to AgNP, despite not being directly (cyto)toxic to these cells, had the potential to alter immune cell responses. The findings underscore the import of assessing immune cell function post-exposure to ENM beyond the standard endpoints such as oxidative stress and cytotoxicity. In addition, these findings further illustrate the importance of understanding the underlying molecular mechanisms of ENM-cellular interactions, particularly in the immune system.