Department of Pollutants and Health, National Institute for Research and Safety, 54519 Vandoeuvre-les-Nancy, France.
Toxicol Lett. 2012 May 5;210(3):267-75. doi: 10.1016/j.toxlet.2012.02.004. Epub 2012 Feb 10.
Due to advances in nanotechnology, exposure to particle compounds in the workplace has become unavoidable. Assessment of their toxicity on health is an important occupational safety issue. This study was conducted in mice to investigate the toxicological effects of submicron and nano-iron oxide particles on pulmonary immune defences. In that purpose, we explored for the first time, inflammatory and immune responses in lung-associated lymph nodes. For each particle type, mice received either a single intratracheal instillation at different concentrations (250, 375, or 500μg/mouse) or four repeated instillations at 500μg/mouse each. Cytokine production, inflammatory and innate immune response, and humoral immune response were respectively assessed 1, 2, and 6 days after particle exposures. Both types of particles induced lung inflammation associated with increased cytokine productions in lymph node cell cultures and decreased pulmonary immune responses against sheep erythrocytes. Natural killer activity was not modified by particles. In comparison to single instillation, repeated instillations resulted in a reduction of inflammatory cell numbers in both bronchoalveolar lavages and pulmonary parenchyma. Moreover, the single instillation model demonstrated that, for a same dose, nano-iron oxide particles produced higher levels of inflammation and immunodepression than their submicron-sized counterparts.
由于纳米技术的进步,工作场所中颗粒化合物的暴露已不可避免。评估其对健康的毒性是一个重要的职业安全问题。本研究在小鼠中进行,旨在研究亚微米和纳米氧化铁颗粒对肺免疫防御的毒理学影响。为此,我们首次探索了肺相关淋巴结中的炎症和免疫反应。对于每种颗粒类型,小鼠接受单次气管内滴注不同浓度(250、375 或 500μg/只)或四次重复滴注 500μg/只。颗粒暴露后 1、2 和 6 天分别评估细胞因子产生、炎症和先天免疫反应以及体液免疫反应。两种类型的颗粒均引起肺炎症,导致淋巴结细胞培养中细胞因子产生增加,对绵羊红细胞的肺免疫反应降低。颗粒未改变自然杀伤活性。与单次滴注相比,重复滴注导致支气管肺泡灌洗液和肺实质中的炎症细胞数量减少。此外,单次滴注模型表明,对于相同剂量,纳米氧化铁颗粒比其亚微米级颗粒产生更高水平的炎症和免疫抑制。