a Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen , Essen , Germany.
b Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA) , Bochum , Germany , and.
Nanotoxicology. 2016 Dec;10(10):1492-1502. doi: 10.1080/17435390.2016.1235740. Epub 2016 Sep 27.
The inhalation of particles and their exposure to the bronchi and alveoli constitute a major public health risk. Chemical as well as particle-related properties are important factors for the biological response but are difficult to separate from each other. Barium sulfate is a completely inert chemical compound, therefore it is ideally suited to separate these two factors. The biological response of rat alveolar macrophages (NR8383) was analyzed after exposure to barium sulfate particles with three different diameters (40 nm, 270 nm, and 1.3 μm, respectively) for 24 h in vitro (particle concentrations from 12.5 to 200 μg mL). The particles were colloidally stabilized as well as fluorescently-labeled by carboxymethylcellulose, conjugated with 6-aminofluorescein. All kinds of barium sulfate particles were efficiently taken up by NR8383 cells and found inside endo-lysosomes, but never in the cell nucleus. Neither an inflammatory nor a cytotoxic response was detected by the ability of dHL-60 and NR8383 cells to migrate towards a chemotactic gradient (conditioned media of NR8383 cells) and by the release of inflammatory mediators (CCL2, TNF-α, IL-6). The particles neither caused apoptosis (up to 200 μg mL) nor necrosis (up to 100 μg mL). As only adverse reaction, necrosis was found at a concentration of 200 μg mL of the largest barium sulfate particles (1.3 μm). Barium sulfate particles are ideally suited as bioinert control to study size-dependent effects such as uptake mechanisms of intracellular distributions of pure particles, especially in nanotoxicology.
吸入颗粒并使其暴露于支气管和肺泡中是一个主要的公共健康风险。化学性质以及与颗粒有关的性质是生物反应的重要因素，但难以将它们彼此分离。硫酸钡是一种完全惰性的化学化合物，因此非常适合将这两个因素分开。分析了大鼠肺泡巨噬细胞（NR8383）在体外暴露于三种不同直径（分别为 40nm、270nm 和 1.3μm）的硫酸钡颗粒 24 小时后的生物反应（颗粒浓度为 12.5 至 200μg mL）。通过羧甲基纤维素将颗粒胶态稳定化并荧光标记，与 6-氨基荧光素缀合。NR8383 细胞能够有效地摄取所有种类的硫酸钡颗粒，并在内涵体溶酶体中发现，但从未在细胞核中发现。通过 dHL-60 和 NR8383 细胞向趋化梯度（NR8383 细胞的条件培养基）迁移的能力以及释放炎症介质（CCL2、TNF-α、IL-6），均未检测到炎症或细胞毒性反应。颗粒既不会引起细胞凋亡（高达 200μg mL），也不会引起细胞坏死（高达 100μg mL）。只有在最大硫酸钡颗粒（1.3μm）浓度为 200μg mL 时才发现坏死。硫酸钡颗粒是作为生物惰性对照的理想选择，可以研究大小依赖性效应，例如纯颗粒的细胞内分布的摄取机制，特别是在纳米毒理学中。
