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银纳米粒子在小鼠骨髓来源树突状细胞中的毒性:对表型的影响。

Toxicity of silver nanoparticles in mouse bone marrow-derived dendritic cells: Implications for phenotype.

机构信息

Department of Physiology, University Center of Health Sciences (CUCS), University of Guadalajara, Jalisco, Mexico.

Department of Health Sciences, Los Altos University Center (CUAltos), University of Guadalajara, Tepatitlan de Morelos, Jalisco, Mexico.

出版信息

J Immunotoxicol. 2019 Dec;16(1):54-62. doi: 10.1080/1547691X.2019.1584652. Epub 2019 Apr 2.

Abstract

Silver nanoparticles (AgNP) are one of the most studied nanoparticles due to their anti-bacterial, -fungal, -viral, -parasitic, and -inflammatory properties. This raises the need to evaluate the toxicity and biological effects of AgNP in the immune system in order to develop new safer biomedical products. In this study, an AgNP formulation currently approved for veterinary applications was applied to mouse bone marrow-derived dendritic cells (BMDC), considered important antigen-presenting cells of the immune system, to evaluate cytotoxicity, genotoxicity, and any significant influence on expression of cellular markers associated with BMDC phenotype and maturation status. The results showed that after 12 h of AgNP exposure, a significant decrease in BMDC viability occurred at the highest concentration tested (1.0 µg AgNP/ml) and at lower doses, the cells maintained membrane integrity and metabolic activity. DNA damage was not significant with any AgNP level aside from the 1.0 µg AgNP/ml level. Regarding phenotype, no differences in expression of CD40 (co-stimulatory molecule highly present in mature BMDC) or in CD273 (a marker for inhibitory T-cell response) were observed. The current results showed that the toxicity of this AgNP formulation was dose-related. The findings also suggest BMDC could maintain structural conservation of co-stimulatory/co-inhibitory surface molecules after 12 h of exposure to this AgNP. This work represents the first step in identifying the toxic effects of this AgNP formulation on dendritic cells.

摘要

银纳米粒子(AgNP)是研究最多的纳米粒子之一,因为它们具有抗细菌、抗真菌、抗病毒、抗寄生虫和抗炎特性。这就需要评估 AgNP 在免疫系统中的毒性和生物学效应,以便开发新的更安全的生物医学产品。在这项研究中,一种目前批准用于兽医应用的 AgNP 制剂被应用于小鼠骨髓来源的树突状细胞(BMDC),BMDC 被认为是免疫系统中重要的抗原呈递细胞,以评估细胞毒性、遗传毒性以及对与 BMDC 表型和成熟状态相关的细胞标志物表达的任何显著影响。结果表明,在 AgNP 暴露 12 小时后,在最高测试浓度(1.0μg AgNP/ml)和较低剂量下,BMDC 的活力显著下降,细胞保持膜完整性和代谢活性。除了 1.0μg AgNP/ml 水平外,任何 AgNP 水平都没有明显的 DNA 损伤。关于表型,除了 1.0μg AgNP/ml 水平外,CD40(成熟 BMDC 中高度存在的共刺激分子)或 CD273(抑制性 T 细胞反应的标志物)的表达没有差异。目前的结果表明,这种 AgNP 制剂的毒性与剂量有关。研究结果还表明,BMDC 在暴露于这种 AgNP 12 小时后,仍能保持共刺激/共抑制表面分子的结构保守性。这项工作代表了确定这种 AgNP 制剂对树突状细胞的毒性作用的第一步。

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