PMID- 25780270 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 0008-6223 (Print) IS - 0008-6223 (Linking) VI - 78 DP - 2014 Nov 1 TI - Multi-walled carbon nanotube length as a critical determinant of bioreactivity with primary human pulmonary alveolar cells. PG - 26-37 AB - 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 microm in length) induced significantly greater responses from the epithelial cells, whilst AM were particularly susceptible to long MWCNTs (~20 microm). 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. FAU - Sweeney, Sinbad AU - Sweeney S AD - Lung Cell Biology, Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK. FAU - Berhanu, Deborah AU - Berhanu D AD - 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. FAU - Misra, Superb K AU - Misra SK AD - 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. FAU - Thorley, Andrew J AU - Thorley AJ AD - Lung Cell Biology, Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK. FAU - Valsami-Jones, Eugenia AU - Valsami-Jones E AD - 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. FAU - Tetley, Teresa D AU - Tetley TD AD - Lung Cell Biology, Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK. LA - eng GR - U19 ES019536/ES/NIEHS NIH HHS/United States PT - Journal Article PL - United States TA - Carbon N Y JT - Carbon JID - 101204394 PMC - PMC4357847 MID - NIHMS665872 EDAT- 2015/03/18 06:00 MHDA- 2015/03/18 06:01 PMCR- 2015/11/01 CRDT- 2015/03/18 06:00 PHST- 2015/03/18 06:00 [entrez] PHST- 2015/03/18 06:00 [pubmed] PHST- 2015/03/18 06:01 [medline] PHST- 2015/11/01 00:00 [pmc-release] AID - 10.1016/j.carbon.2014.06.033 [doi] PST - ppublish SO - Carbon N Y. 2014 Nov 1;78:26-37. doi: 10.1016/j.carbon.2014.06.033.