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Evaluation of the skin-sensitizing potential of gold nanoparticles and the impact of established dermal sensitivity on the pulmonary immune response to various forms of gold.
Nanotoxicology ( IF 5 ) Pub Date : 2020-09-10 , DOI: 10.1080/17435390.2020.1808107
K A Roach 1 , S E Anderson 1 , A B Stefaniak 2 , H L Shane 1 , G R Boyce 1 , J R Roberts 1
Affiliation  

Abstract

Gold nanoparticles (AuNP) are largely biocompatible; however, many studies have demonstrated their potential to modulate various immune cell functions. The potential allergenicity of AuNP remains unclear despite the recognition of gold as a common contact allergen. In these studies, AuNP (29 nm) dermal sensitization potential was assessed via Local Lymph Node Assay (LLNA). Soluble gold (III) chloride (AuCl3) caused lymph node (LN) expansion (SI 10.9), whereas bulk particles (Au, 942 nm) and AuNP did not. Next, the pulmonary immune effects of AuNP (10, 30, 90 µg) were assessed 1, 4, and 8 days post-aspiration. All markers of lung injury and inflammation remained unaltered, but a dose-responsive increase in LN size was observed. Finally, mice were dermally-sensitized to AuCl3 then aspirated once, twice, or three times with Au or AuNP in doses normalized for mass or surface area (SA) to assess the impact of existing contact sensitivity to gold on lung immune responses. Sensitized animals exhibited enhanced responsivity to the metal, wherein subsequent immune alterations were largely conserved with respect to dose SA. The greatest increase in bronchoalveolar lavage (BAL) lymphocyte number was observed in the high dose group – simultaneous to preferential expansion of BAL/LN CD8+ T-cells. Comparatively, the lower SA-based doses of Au/AuNP caused more modest elevations in BAL lymphocyte influx (predominantly CD4+ phenotype), exposure-dependent increases in serum IgE, and selective expansion/activation of LN CD4+ T-cells and B-cells. Overall, these findings suggest that AuNP are unlikely to cause sensitization; however, established contact sensitivity to gold may increase immune responsivity following pulmonary AuNP exposure.



中文翻译:

评估金纳米颗粒的皮肤致敏性以及已建立的皮肤敏感性对各种形式的金的肺免疫反应的影响。

摘要

金纳米粒子(AuNP)在很大程度上具有生物相容性。但是,许多研究表明它们具有调节各种免疫细胞功能的潜力。尽管金被认为是一种常见的接触性过敏原,但AuNP的潜在致敏性仍不清楚。在这些研究中,通过局部淋巴结测定(LLNA)评估了AuNP(29 nm)皮肤致敏性。可溶性氯化金(III)(AuCl 3)引起淋巴结(LN)膨胀(SI 10.9),而散装颗粒(Au,942 nm)和AuNP却没有。接下来,在抽吸后1、4和8天评估AuNP(10、30、90 µg)的肺免疫效果。肺损伤和炎症的所有标记均未改变,但观察到LN大小呈剂量反应性增加。最后,将小鼠对AuCl 3进行皮肤敏化然后用Au或AuNP以质量或表面积(SA)归一化的剂量抽吸一次,两次或三次,以评估现有的对金的接触敏感性对肺免疫反应的影响。致敏的动物对金属的反应性增强,其中,相对于剂量SA,后续的免疫改变在很大程度上得以保留。在高剂量组中观察到支气管肺泡灌洗(BAL)淋巴细胞数量的最大增加–同时优先扩增BAL / LN CD8 + T细胞。相比之下,较低的基于SA的Au / AuNP剂量导致BAL淋巴细胞流入(主要是CD4 +表型)适度升高,血清IgE依赖于暴露的增加以及LN CD4 + T细胞和B细胞的选择性扩增/激活。总体而言,这些发现表明AuNP不太可能引起过敏。然而,

更新日期:2020-10-30
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