Functional consequences for primary human alveolar macrophages following treatment with long, but not short, multiwalled carbon nanotubes
Authors Sweeney S, Grandolfo D, Ruenraroengsak P, Tetley T
Received 21 November 2014
Accepted for publication 5 February 2015
Published 23 April 2015 Volume 2015:10(1) Pages 3115—3129
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Thomas J Webster
Sinbad Sweeney, Davide Grandolfo, Pakatip Ruenraroengsak, Teresa D Tetley
Lung Cell Biology, Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, London, UK
Purpose: 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 who may be intentionally (via therapeutic applications) or unintentionally exposed to these nanomaterials.
Keywords: nanotechnology, MWCNTs, alveolar macrophages, cytokines, phagocytosis, bioreactivity
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