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Sinbad Sweeney, Davide Grandolfo, Pakatip Ruenraroengsak, Teresa D TetleyLung Cell Biology, Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, London, UKPurpose: Multiwalled carbon nanotubes (MWCNTs) are a potential human health hazard, primarily via inhalation. In the lung, alveolar macrophages (AMs) provide the first line of immune cellular defense against inhaled materials. We hypothesized that, 1 and 5 days after treating AMs with short (0.6 µm in length; MWCNT-0.6 µm) and long (20 µm in length; MWCNT-20 µm) MWCNTs for 24 hours, AMs would exhibit increased markers of adverse bioreactivity (cytokine release and reactive oxygen species generation) while also having a modified functional ability (phagocytosis and migration).Methods: Primary human AMs were treated with short and long MWCNTs for 24 hours, 1 and 5 days after which toxicity end points, including cell death, reactive oxygen species generation, and inflammatory mediator release, were measured. AM functional end points involving phagocytic ability and migratory capacity were also measured.Results: AM viability was significantly decreased at 1 and 5 days after treatment with MWCNT-20 µm, while superoxide levels and inflammatory mediator release were significantly increased. At the same time, there was reduced phagocytosis and migratory capacity alongside increased expression of MARCO; this coincided with frustrated phagocytosis observed by scanning electron microscopy. In contrast, the adverse bioreactivity of the shorter MWCNT-0.6 µm with AMs (and any resulting reduction in AM functional ability) was substantially less marked or absent altogether.Conclusion: This study shows that after 24-hour treatment with long, but not short, MWCNTs, AM function is severely affected up to 5 days after the initial exposure. This has potentially significant pathophysiological consequences for individuals

Sinbad Sweeney, Davide Grandolfo, Pakatip Ruenraroengsak, Teresa D TetleyLung Cell Biology, Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, London, UKPurpose: Multiwalled carbon nanotubes (MWCNTs) are a potential human health hazard, primarily via inhalation. In the lung, alveolar macrophages (AMs) provide the first line of immune cellular defense against inhaled materials. We hypothesized that, 1 and 5 days after treating AMs with short (0.6 µm in length; MWCNT-0.6 µm) and long (20 µm in length; MWCNT-20 µm) MWCNTs for 24 hours, AMs would exhibit increased markers of adverse bioreactivity (cytokine release and reactive oxygen species generation) while also having a modified functional ability (phagocytosis and migration).Methods: Primary human AMs were treated with short and long MWCNTs for 24 hours, 1 and 5 days after which toxicity end points, including cell death, reactive oxygen species generation, and inflammatory mediator release, were measured. AM functional end points involving phagocytic ability and migratory capacity were also measured.Results: AM viability was significantly decreased at 1 and 5 days after treatment with MWCNT-20 µm, while superoxide levels and inflammatory mediator release were significantly increased. At the same time, there was reduced phagocytosis and migratory capacity alongside increased expression of MARCO; this coincided with frustrated phagocytosis observed by scanning electron microscopy. In contrast, the adverse bioreactivity of the shorter MWCNT-0.6 µm with AMs (and any resulting reduction in AM functional ability) was substantially less marked or absent altogether.Conclusion: This study shows that after 24-hour treatment with long, but not short, MWCNTs, AM function is severely affected up to 5 days after the initial exposure. This has potentially significant pathophysiological consequences for individuals