Size effects of single-walled carbon nanotubes on in vivo and in vitro pulmonary toxicity.
Size effects of single-walled carbon nanotubes on in vivo and in vitro pulmonary toxicity.
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DOI：
10.3109/08958378.2015.1026620
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发表时间：
2015-03
影响因子：
2.1
通讯作者：
Honda K
中科院分区：
文献类型：
--
作者：
Fujita K;Fukuda M;Endoh S;Maru J;Kato H;Nakamura A;Shinohara N;Uchino K;Honda K
为了阐明尺寸对单壁碳纳米管（SWCNTs）肺毒性的影响，我们制备了两种类型的分散的SWCNTs，即具有短线形形状的相对薄的束（CNT-1）和具有长线形形状的粗束（CNT-2），并使用NR 8383大鼠肺泡巨噬细胞进行大鼠肺内滴注试验和体外基于细胞的测定。总蛋白水平、MIP-1α表达、BALF中细胞计数和组织病理学检查显示，CNT-1引起肺部炎症和恢复较慢，而CNT-2在滴注后不久就引起急性肺部炎症。全面的基因表达分析证实，CNT-1诱导的基因与滴注后7或30天的炎症反应、细胞增殖和免疫系统过程密切相关。许多基因显着上调或下调CNT-2滴注后1天。体外实验表明，CNT-1和CNT-2单壁碳纳米管被NR 8383细胞吞噬。CNT-2处理诱导细胞生长抑制、活性氧产生、MIP-1α表达和参与对刺激的响应的几个基因，而CNT-1处理在这些方面没有产生显著影响。这些结果表明，形成为具有短线性形状的相对薄的束的SWCNT引起具有较慢恢复的延迟的肺部炎症。相比之下，具有相对厚的束和长的线性形状的SWCNT敏感地诱导肺泡巨噬细胞中的细胞反应，并在吸入后不久引起急性肺部炎症。我们的结论是单壁碳纳米管的肺毒性是密切相关的束的大小。这些物理参数可用于单壁碳纳米管的风险评估和管理。
To elucidate the effect of size on the pulmonary toxicity of single-wall carbon nanotubes (SWCNTs), we prepared two types of dispersed SWCNTs, namely relatively thin bundles with short linear shapes (CNT-1) and thick bundles with long linear shapes (CNT-2), and conducted rat intratracheal instillation tests and in vitro cell-based assays using NR8383 rat alveolar macrophages. Total protein levels, MIP-1α expression, cell counts in BALF, and histopathological examinations revealed that CNT-1 caused pulmonary inflammation and slower recovery and that CNT-2 elicited acute lung inflammation shortly after their instillation. Comprehensive gene expression analysis confirmed that CNT-1-induced genes were strongly associated with inflammatory responses, cell proliferation, and immune system processes at 7 or 30 d post-instillation. Numerous genes were significantly upregulated or downregulated by CNT-2 at 1 d post-instillation. In vitro assays demonstrated that CNT-1 and CNT-2 SWCNTs were phagocytized by NR8383 cells. CNT-2 treatment induced cell growth inhibition, reactive oxygen species production, MIP-1α expression, and several genes involved in response to stimulus, whereas CNT-1 treatment did not exert a significant impact in these regards. These results suggest that SWCNTs formed as relatively thin bundles with short linear shapes elicited delayed pulmonary inflammation with slower recovery. In contrast, SWCNTs with a relatively thick bundle and long linear shapes sensitively induced cellular responses in alveolar macrophages and elicited acute lung inflammation shortly after inhalation. We conclude that the pulmonary toxicity of SWCNTs is closely associated with the size of the bundles. These physical parameters are useful for risk assessment and management of SWCNTs.
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影响因子：
1.7
作者：
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通讯作者：
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作者：
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