Macrophage fusion caused by particle instillation

Our plain-English summary of Macrophage fusion caused by particle instillation, by K.L. Trout, A. Holian (Current Research in Toxicology, 2020).

The study

• Authors: K.L. Trout, A. Holian
• Journal: Current Research in Toxicology
• Published: 2020;1:42-47
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Multinucleated giant cells (MGC) are formed by fusion of macrophages in pathological conditions. These are often studied in the context of the foreign body response to biomaterial implants, but MGC formation is rarely assessed in response to inorganic particles in the lungs. Therefore, a major objective of this study was to quantitatively compare in vivo macrophage fusion resulting from exposure to a spectrum of micron- and nano-sized particles from both environmental and engineered origin, including crystalline silica, multiwalled carbon nanotubes, titanium nanobelts, and crocidolite asbestos.

Methods: Groups of C57Bl/6 mice were instilled with inorganic particles or PBS control. Lung cells were collected by lavage after one week for cell differentials, quantification of macrophage fusion, and microscopic observation of particle uptake.

Results: MGC were present in lungs of all mice exposed to particles; no MGC were found in control mice. Asbestos exposure resulted in significant macrophage fusion, which coincided with significantly increased total lavage cells and percent neutrophils. Microscopic observations show particle internalization in MGC and a unique case of potential heterotypic fusion of macrophages with neutrophils.

Conclusion: MGC can form in the lungs of mice within a relatively short one-week time period after particle exposure. The number of MGC was sufficient for quantification and statistical analysis, indicating that MGC formation was more than simply a rare chance occurrence. Observations of particles within MGC warrants further investigation of MGC involvement in inflammation and particle clearance.

In plain English

This was a laboratory experiment in mice, not a study of people. The authors put one of four particle types into the lungs of male and female C57Bl/6 mice: crystalline silica (1 mg per mouse), multiwalled carbon nanotubes, titanium nanobelts or crocidolite asbestos (50 μg per mouse each). A comparison group received a saline (PBS) solution. Groups had 4 to 9 mice. After 7 days the authors washed cells out of the lungs and counted multinucleated giant cells, which form when immune cells called macrophages fuse together. No giant cells were found in control mice, while measurable numbers appeared in all particle-exposed mice. Crocidolite asbestos produced the most giant cells, and the asbestos group's fusion level was statistically significantly greater than zero. Asbestos-exposed mice also had significantly more total cells recovered by lung washing (lavage), and a higher percentage of neutrophils, than controls. Other particles showed similar trends that were not statistically significant. Particles of all four types were seen inside giant cells. The authors concluded that giant cells can form within 7 days of particle exposure and called for further study.

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 (mice given a single dose of particles into the lungs, examined after 7 days)
• Who was studied: Male and female C57Bl/6 laboratory mice aged 8 to 12 weeks, University of Montana. There were 4 mice in the PBS control group, 4 in the silica group, 9 in the carbon nanotube group, 7 in the titanium nanobelt group and 8 in the crocidolite asbestos group.
• Exposure: A single dose by oropharyngeal aspiration (liquid placed at the back of the throat and breathed into the lungs). Doses were crystalline silica 1 mg per mouse, and 50 μg per mouse for each of multiwalled carbon nanotubes, titanium nanobelts and crocidolite asbestos (an amphibole fiber, 160 nm diameter, 5 μm long). Controls received PBS.
• Main results:
  • No multinucleated giant cells were found in the lung washings of PBS control mice. Measurable numbers appeared in all particle-exposed mice.
  • Crocidolite asbestos produced the highest number of giant cells. The asbestos group's percent fusion was statistically significantly greater than zero (p less than 0.05). The article's text gives no numeric fusion values; these appear only in a figure.
  • In asbestos-exposed mice, the total number of cells recovered by lung lavage and the percent neutrophils were significantly higher than in PBS controls.
  • Mice exposed to the other particles showed similar increasing trends in total cells and neutrophils, but these were not statistically significant.
  • Giant cells were seen containing particles of every type tested.
  • In one asbestos-exposed mouse, a single cell appeared to contain nuclei from both macrophages and neutrophils in a shared cell body. The authors described this as possible fusion of the two cell types.
• The authors' conclusion: The authors concluded that giant cells can form in the lung within 7 days of exposure to inorganic particles, with significant macrophage fusion after asbestos exposure. They stated that further investigation of the role of giant cells in inflammation and particle clearance is warranted.
• Limitations the authors state:
  • Only one clear example of the possible macrophage-neutrophil fused cell was seen, so the authors said confirmatory studies are needed.
  • Other cells of this type could not be identified with confidence because of unclear staining and overlapping nuclei.
  • Single doses were chosen based on earlier research. The authors noted this matters when drawing conclusions about relative particle toxicity, which was not the main aim of the study.
  • The authors could not tell whether particles were taken up before or after macrophages fused into giant cells.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Crystalline, Crocidolite, Asbestos Exposure, Inflammation.

Related studies

• Macrophage phagocytic activity and cell phagocytic capacity following intratracheal instillation of a comixture of asbestos fibers — I. Trosic, M. Matausic-Pisl, et al. (1995)
• Bronchiolitis caused by occupational and ambient atmospheric particles — A. Churg, J.L. Wright (2003)
• Protective effect of natural flavonoids on rat peritoneal macrophages injury caused by asbestos fibers — V.A. Kostyuk, A.I. Potapovich, et al. (1996)
• Asbestos fibers and silica particles stimulate rat alveolar macrophages to release tumor necrosis factor. Autoregulatory role of leukotriene B4 — C.M. Dubois, E. Bissonnette, et al. (1989)
• Production of arachidonic acid metabolites by macrophages exposed in vitro to asbestos, carbonyl iron particles, or calcium ionophore — S. Kouzan, A.R. Brody, et al. (1985)
• Stimulation of oxidant production in alveolar macrophages by pollutant and latex particles — G.E. Hatch, D.E. Gardner, et al. (1980)

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