title: Multi-walled carbon nanotube length as a critical determinant of bioreactivity with primary human pulmonary alveolar cells.
abstract: Multiwalled carbon nanotube (MWCNT) length is suggested to critically determine their pulmonary toxicity. This stems fromin vitroandin vivorodent studies andin vitrohuman 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.
authors.affiliation: Lung Cell Biology, Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK.
authors.forename: Sinbad
authors.initials: S
authors.lastname: Sweeney
authors.affiliation: Physical Sciences Department, Kingsborough Community College, City University of New York, 2001 Oriental Boulevard, New York, NY 11235 ; Earth Sciences, Natural History Museum, Cromwell Road, London SW7 5BD, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Berhanu
authors.affiliation: School of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B5 2TT, UK ; Earth Sciences, Natural History Museum, Cromwell Road, London SW7 5BD, UK.
authors.forename: Superb K
authors.initials: SK
authors.lastname: Misra
authors.affiliation: Lung Cell Biology, Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Thorley
authors.affiliation: School of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B5 2TT, UK ; Earth Sciences, Natural History Museum, Cromwell Road, London SW7 5BD, UK.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Valsami-Jones
authors.affiliation: Lung Cell Biology, Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK.
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Tetley