Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice.
Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice.
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DOI：
10.1186/1743-8977-6-2
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发表时间：
2009-01-12
影响因子：
10
通讯作者：
Wallin H
中科院分区：
文献类型：
--
作者：
Jacobsen NR;Møller P;Jensen KA;Vogel U;Ladefoged O;Loft S;Wallin H
在载脂蛋白E敲除小鼠（ApoE-/-）的肺效应敏感模型中，研究了5种不同类型纳米颗粒的毒性和炎症潜力。我们研究了炭黑（CB）滴注或吸入Printex 90对ApoE-/-和C57小鼠的影响，并比较了CB滴注对ApoE-/-和C57小鼠的影响。肺暴露后3和24 h，通过肺组织中细胞因子mRNA水平、细胞组成、遗传毒性、支气管肺泡灌洗液中蛋白质和乳酸脱氢酶活性来评估炎症。首先，我们发现ApoE-/-小鼠气管内灌注CB引起的肺毒性远远大于C57小鼠。其次，我们发现，就ApoE-/-小鼠肺部炎症而言，注射CB比吸入假定相同剂量的CB毒性更大。第三，我们比较了三种碳质颗粒在ApoE-/-小鼠体内的灌注效果；碳纳米管，富勒烯C60 （C60）和单壁碳纳米管（SWCNT）以及金粒子和量子点（QDs）。对注入介质的表征表明，所有颗粒都以团聚体和团聚体的形式传递。在swcnts、CB和QDs灌注后3 h和24 h，肺组织中Il-6、Mip-2和Mcp-1 mRNA均显著升高。BAL细胞DNA损伤、BAL细胞中性粒细胞及BAL液蛋白含量均显著升高。金和C60颗粒引起的炎症反应要弱得多。我们的数据表明，ApoE-/-模型对评估颗粒诱导的炎症是敏感的。总体而言，QDs的影响最大，其次是CB和swcnts， C60和金的炎症和dna损伤最小。然而，与其他粒子相比，金的使用质量剂量要低得多。量子点的强效应可能是由于Cd的释放。注射剂量的表面积与低毒性颗粒的炎症反应密切相关。
The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE-/-). We studied the effects instillation or inhalation Printex 90 of carbon black (CB) and compared CB instillation in ApoE-/- and C57 mice. Three and 24 h after pulmonary exposure, inflammation was assessed by mRNA levels of cytokines in lung tissue, cell composition, genotoxicity, protein and lactate dehydrogenase activity in broncho-alveolar lavage (BAL) fluid. Firstly, we found that intratracheal instillation of CB caused far more pulmonary toxicity in ApoE-/- mice than in C57 mice. Secondly, we showed that instillation of CB was more toxic than inhalation of a presumed similar dose with respect to inflammation in the lungs of ApoE-/- mice. Thirdly, we compared effects of instillation in ApoE-/- mice of three carbonaceous particles; CB, fullerenes C60 (C60) and single walled carbon nanotubes (SWCNT) as well as gold particles and quantum dots (QDs). Characterization of the instillation media revealed that all particles were delivered as agglomerates and aggregates. Significant increases in Il-6, Mip-2 and Mcp-1 mRNA were detected in lung tissue, 3 h and 24 h following instillation of SWCNT, CB and QDs. DNA damage in BAL cells, the fraction of neutrophils in BAL cells and protein in BAL fluid increased statistically significantly. Gold and C60 particles caused much weaker inflammatory responses. Our data suggest that ApoE-/- model is sensitive for evaluating particle induced inflammation. Overall QDs had greatest effects followed by CB and SWCNT with C60 and gold being least inflammatory and DNA-damaging. However the gold was used at a much lower mass dose than the other particles. The strong effects of QDs were likely due to Cd release. The surface area of the instilled dose correlated well the inflammatory response for low toxicity particles.
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