Lung exposure to nanoparticles modulates an asthmatic response in a mouse model

Lung exposure to nanoparticles modulates an asthmatic response in a mouse model
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DOI:
10.1183/09031936.00168509
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发表时间:
2011-02-01
影响因子:
24.3
通讯作者:
Hoet, P. H. M.
Hoet, P. H. M.
中科院分区:
医学1区
文献类型:
--
作者:
Hussain, S.;Vanoirbeek, J. A. J.;Hoet, P. H. M.

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本研究的目的是调查二氧化钛(TiO 2)或金(Au)纳米粒子(NPs)在二异氰酸酯诱导的哮喘小鼠模型中的哮喘反应的调制。在第1天和第8天,BALB/c小鼠接受0.3%甲苯二异氰酸酯(TDI)或溶剂丙酮-橄榄油(AOO)的双耳背(20 μ L)。在第14天,对小鼠口咽给药40 μ L NP悬浮液(0.4 mg.mL(-1)(类似于0.8 mg.kg(-1))TiO 2或Au)。1天后(第15天),小鼠接受0.01%TDI(20 μ L)的口咽攻击。在第16天,评估气道高反应性(AHR)、支气管肺泡灌洗(BAL)细胞和细胞因子分析、肺组织学和总血清免疫球蛋白EdNP暴露于致敏小鼠导致AHR增加2倍(TiO 2)或3倍(Au),并且BAL总细胞计数增加3倍(TiO 2)或5倍(Au),主要包括中性粒细胞和巨噬细胞。通过能量色散X射线光谱法鉴定由BAL巨噬细胞摄取的NP。组织学分析显示水肿、上皮损伤和炎症增加。总之,这些结果表明,肺内低剂量的TiO 2或Au NPs可加重二异氰酸酯诱导的哮喘小鼠模型的肺部炎症和AHR。
The aim of this study was to investigate the modulation of an asthmatic response by titanium dioxide (TiO2) or gold (Au) nanoparticles (NPs) in a murine model of diisocyanate-induced asthma.On days 1 and 8, BALB/c mice received 0.3% toluene diisocyanate (TDI) or the vehicle acetone-olive oil (AOO) on the dorsum of both ears (20 mu L). On day 14, the mice were oropharyngeally dosed with 40 mu L of a NP suspension (0.4 mg.mL(-1) (similar to 0.8 mg.kg(-1)) TiO2 or Au). 1 day later (day 15), the mice received an oropharyngeal challenge with 0.01% TDI (20 mu L). On day 16, airway hyperreactivity (AHR), bronchoalveolar lavage (BAL) cell and cytokine analysis, lung histology, and total serum immunoglobulin E were assessed.NP exposure in sensitised mice led to a two-(TiO2) or three-fold (Au) increase in AHR, and a three-(TiO2) or five-fold (Au) increase in BAL total cell counts, mainly comprising neutrophils and macrophages. The NPs taken up by BAL macrophages were identified by energy dispersive X-ray spectroscopy. Histological analysis revealed increased oedema, epithelial damage and inflammation.In conclusion, these results show that a low, intrapulmonary doses of TiO2 or Au NPs can aggravate pulmonary inflammation and AHR in a mouse model of diisocyanate-induced asthma.