Abstract
PurposeMultiwalled 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).MethodsPrimary 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.ResultsAM 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.ConclusionThis 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.
Highlights
The nanotechnology sector has become an important and rapidly growing global industry, developing and producing a vast array of nanomaterials
This dose of multiwalled carbon nanotubes (MWCNTs) was chosen as we previously found it had maximal bioreactivity with sufficient viability, in Alveolar macrophages (AMs) following a 24-hour treatment, which we believed would allow us to examine whether AMs could maintain their immune functionality following treatment with these nanomaterials.[21]
Protruding MWCNTs were accompanied by membrane blebbing, severe membrane distortion, and multiple AM recruitment, suggesting MWCNT-induced frustrated phagocytosis (Figure 1D)
Summary
The nanotechnology sector has become an important and rapidly growing global industry, developing and producing a vast array of nanomaterials (materials with at least one external dimension ,100 nm, [ISO/TS: 27687:2008]). Engineered multiwalled carbon nanotubes (MWCNTs) are one such nanomaterial whose production capacity is estimated at several thousand tons yearly.[1] MWCNTs offer high strength-to-weight ratios, tensile strength, conductivity, and thermal stability. Occurring with diameters in the lownanometer range and lengths in the high-micrometer range, MWCNTs are being applied in industries such as electronics, automobile, aerospace, and nanomedicine (eg, drug/gene delivery and scaffolds for tissue engineering).[2] Products already incorporating MWCNTs include computer components, aircraft structural components, and sporting equipment. The full terms of the License are available at http://creativecommons.org/licenses/by/4.0/.
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