Length-dependent pathogenic effects of nickel nanowires in the lungs and the peritoneal cavity

Our plain-English summary of Length-dependent pathogenic effects of nickel nanowires in the lungs and the peritoneal cavity, by C.A. Poland, F. Byrne, W.S. Cho, et al (Nanotoxicology, 2012).

The study

• Authors: C.A. Poland, F. Byrne, W.S. Cho, A. Prina-Mello, F.A. Murphy, G.L. Davies, J.M. Coey, Y. Gounko, R. Duffin, Y. Volkov, K. Donaldson
• Journal: Nanotoxicology
• Published: 2012;6:899-911
• Cited by: 54 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The use of fibre-shaped nanomaterials in commercial applications has met with concern that they could cause health effects similar to those seen with pathogenic fibres such as certain forms of asbestos. Of the attributes which form the fibre pathogenicity paradigm, fibre length is thought to be a critical factor in determining fibre toxicity. We have previously shown that carbon nanotubes display such length-dependent pathogenicity but it remains unclear if other forms of fibrous nanomaterials conform to the fibre pathogenicity paradigm. As such, our aim is to determine the generality of this hypothesis by asking whether a radically different form of fibrous nanomaterial, nickel nanowires, show length-dependent pathogenicity. Our results indicate that nickel nanowires synthesised to be predominantly long (>20 μm) show the ability to elicit strong inflammation in the mouse peritoneal model in a dose-dependent manner; inflammation or fibrosis was not seen with the short (<5 μm) nanowires. This length-dependent response was also seen after lung aspiration and within a macrophage in vitro model adding further weight to the contention that fibre length is an important driver of hazard potential. This may have important implications when considering the hazard posed by fibrous nanomaterials and their regulation in workplaces.

In plain English

This was a laboratory study in mice and in cultured cells testing whether nickel nanowires show length-dependent effects like those described for asbestos and carbon nanotubes. The authors made nickel nanowires of two length ranges, long (mean 24 ± 7 micrometres, 73% above 20 micrometres) and short (mean 4.3 ± 1 micrometres, 77% under 5 micrometres), both about 200 nm in diameter, and also tested a spherical nickel nanoparticle. Female C57BL/6 mice were injected into the peritoneal cavity with 50 micrograms, or given 50 micrograms by pharyngeal aspiration into the lungs; THP-1 macrophages were exposed in vitro. Twenty-four hours after injection, the long nanowires produced a highly significant rise in peritoneal neutrophils and protein (p less than 0.001) compared with vehicle, and significantly greater than the short nanowires and nanoparticles; neutrophil influx rose with dose (r2 = 0.9863). Only the long nanowires produced diaphragm granulomas at 7 days. In the lung, long nanowires caused granulomas with collagen; nanoparticles caused mild diffuse alveolitis. An aqueous extract caused no inflammation. The authors concluded nickel nanowires show length-dependent inflammogenicity.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: animal experiment (mouse intraperitoneal injection and pharyngeal aspiration) combined with an in vitro macrophage cell experiment
• Who was studied: Female C57BL/6 mice aged 8-12 weeks (20-25 g), in groups of three per treatment (six for L-NiNW diaphragm assessment; lung studies N=3 per treatment, N=2 vehicle), plus the human monocytic THP-1 cell line differentiated into macrophages
• Exposure: Long nickel nanowires (mean length 24 ± 7 micrometres), short nickel nanowires (mean 4.3 ± 1 micrometres), both about 200 nm diameter with a 3-4 nm nickel oxide surface layer, and spherical nickel nanoparticles (mean dry diameter 15 nm); 50 micrograms per mouse intraperitoneally (dose range 0.5, 1, 10 and 50 micrograms) or 50 micrograms by lung aspiration; 5 micrograms/ml in vitro
• Main results:
  • Twenty-four hours after intraperitoneal injection of 50 micrograms, long nickel nanowires produced a highly significant increase in lavage neutrophils and total protein compared with controls (p less than 0.001), significantly greater than short nanowires and nickel nanoparticles (p less than 0.001)
  • Seven days after injection, granulomas on the diaphragm mesothelium occurred only with long nickel nanowires; short nanowires and nickel nanoparticles produced no lesions
  • Neutrophil influx at 24 h after intraperitoneal long nanowires followed a straight-line dose response (r2 = 0.9863) across 0.5, 1, 10 and 50 micrograms per mouse; at 7 days the response was markedly reduced with no dose-response and only the 1 microgram dose significantly above vehicle control
  • An aqueous extract of the highest dose (50 micrograms) of long nanowires produced no inflammation, which the authors took as excluding a contribution of soluble nickel ions
  • After lung aspiration of 50 micrograms, BAL neutrophils were elevated in all nickel-exposed groups versus vehicle; at 7 days long nanowires produced cellular granulomas with collagen deposition at terminal bronchioles, nickel nanoparticles produced only mild diffuse alveolitis, and long and short nanowires thickened the alveolar septae to a similar degree
  • In differentiated THP-1 macrophages exposed for 24 h, long nanowires significantly increased IL-1beta and IL-6 (p less than or equal to 0.001) over vehicle control, short nanowires and nickel nanoparticles; nickel nanoparticles also significantly increased TNF-alpha and CCL3
  • Macrophages recovered from the peritoneal cavity fully engulfed short nanowires and nanoparticles, while long nanowires were associated with incomplete (frustrated) phagocytosis
• The authors' conclusion: The authors concluded that, like asbestos and carbon nanotubes, nickel nanowires showed length-dependent inflammogenicity in the mouse peritoneal cavity and length-dependent lung pathology, supporting the applicability of the fibre pathogenicity paradigm to high aspect ratio nanoparticles generally
• Limitations the authors state:
  • The authors stated that the length at which a fibre becomes pathogenic remains undefined and that their data are based only on broad size classes
  • The authors noted caveats in using the peritoneal cavity as a model for the pleural space, including that the pleural space is only notional and fluid-filled with constantly moving surfaces
  • The authors noted that sonication during dispersion caused a small degree of shortening of the nanowires (7% for the long and 4% for the short sample)
  • The authors noted that aspiration delivers a substantial instantaneous dose rate, unlike inhalation
  • The authors stated that further work is needed before the in vitro cytokine responses could serve as a predictive assay for length-dependent effects

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Cavity, Inflammation, Fibrosis, Macrophage.

Related studies

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• Length-dependent pleural inflammation and parietal pleural responses after deposition of carbon nanotubes in the pulmonary airspaces of mice — F.A. Murphy, C.A. Poland, et al. (2013)
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