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

Sinbad Sweeney, Deborah Berhanu, Superb K. Misra, Andrew J. Thorley, Eugenia Valsami-jones, Teresa D. Tetley

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)26-37
JournalCarbon
Volume78
Early online date26 Jun 2014
DOIs
Publication statusPublished - Nov 2014

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