Multi-walled carbon nanotube length as a critical determinant of bioreactivity with primary human pulmonary alveolar cells.

Multi-walled carbon nanotube length as a critical determinant of bioreactivity with primary human pulmonary alveolar cells.
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DOI:
10.1016/j.carbon.2014.06.033
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发表时间:
2014-11-01
期刊:
影响因子:
10.9
通讯作者:
Tetley, Teresa D.
Tetley, Teresa D.
中科院分区:
材料科学2区
文献类型:
--
作者:
Sweeney, Sinbad;Berhanu, Deborah;Misra, Superb K.;Thorley, Andrew J.;Valsami-Jones, Eugenia;Tetley, Teresa D.

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多壁碳纳米管(MWCNT)的长度被认为是决定其肺毒性的关键因素。这源于体外和体内啮齿动物研究以及使用细胞系(通常是癌细胞)的体外人类研究。使用原代人肺细胞的数据很少。我们解决了这一知识差距,使用高度相关的,主要的人类肺泡细胞模型暴露于精确合成和彻底表征的多壁碳纳米管。在这项工作中,转化的人肺泡I型样上皮细胞(TT 1),原代人肺泡II型上皮细胞(ATII)和肺泡巨噬细胞(AM)进行了处理,增加浓度的多壁碳纳米管测量细胞毒性,炎症介质释放和MAP激酶信号。引人注目的是,我们观察到短MWCNTs(长度约为0.6 µm)诱导上皮细胞产生显著更大的反应,而AM对长MWCNTs(长度约为20 µm)特别敏感。介质释放模式的这些差异与每种细胞类型内JNK、p38和ERK 1/2 MAP激酶信号转导的替代概况相关。这项研究,使用高度相关的目标人肺泡细胞和明确定义和表征的多壁碳纳米管,显示出显着的细胞反应的多壁碳纳米管,根据靶细胞类型,以及纵横比的多壁碳纳米管。
Multiwalled carbon nanotube (MWCNT) length is suggested to critically determine their pulmonary toxicity. This stems from in vitro and in vivo rodent studies and in vitro human studies using cell lines (typically cancerous). There is little data using primary human lung cells. We addressed this knowledge gap, using highly relevant, primary human alveolar cell models exposed to precisely synthesized and thoroughly characterized MWCNTs. In this work, transformed human alveolar type-I-like epithelial cells (TT1), primary human alveolar type-II epithelial cells (ATII) and alveolar macrophages (AM) were treated with increasing concentrations of MWCNTs before measuring cytotoxicity, inflammatory mediator release and MAP kinase signalling. Strikingly, we observed that short MWCNTs (~0.6 µm in length) induced significantly greater responses from the epithelial cells, whilst AM were particularly susceptible to long MWCNTs (~20 µm). These differences in the pattern of mediator release were associated with alternative profiles of JNK, p38 and ERK1/2 MAP kinase signal transduction within each cell type. This study, using highly relevant target human alveolar cells and well defined and characterized MWCNTs, shows marked cellular responses to the MWCNTs that vary according to the target cell type, as well as the aspect ratio of the MWCNT.
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