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Multi-walled carbon nanotube length as a critical determinant of bioreactivity with primary human pulmonary alveolar cells
Affiliation:1. Lung Cell Biology, Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK;2. Earth Sciences, Natural History Museum, Cromwell Road, London SW7 5BD, UK;3. Physical Sciences Department, Kingsborough Community College, City University of New York, 2001 Oriental Boulevard, New York, NY 11235, USA;4. School of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B5 2TT, UK;5. Materials Science and Engineering, Indian Institute of Technology-Gandhinagar, Ahmedabad-382424, India;1. Civil Engineering Faculty, Graduate University of Advanced Technology, Haftbagh Exp. Way, Kerman, Iran;2. Civil Engineering Faculty, K.N.Toosi University of Technology, No. 1346, Vali Asr Street, Mirdamad Intersection, Tehran, Iran;3. Department of Concrete Technology, Building and Housing Research Center (BHRC), Pas Farhangian Street, Sheikh Fazlollah Exp. Way, Tehran, Iran
Abstract: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 synthesised and thoroughly characterised 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 characterised 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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