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Fabricating Optical-quality Glass Surfaces to Study Macrophage Fusion
Published on: March 14, 2018
Macrophage fusion caused by particle instillation
Kevin L Trout1, Andrij Holian1
1Department of Biomedical and Pharmaceutical Sciences, University of Montana, 32 Campus Dr, Missoula, MT 59812, United States.
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.
Insights
Multinucleated giant cells (MGC) form in mouse lungs within one week of exposure to various inorganic particles. Asbestos exposure significantly increased MGC formation, indicating their role in particle-induced lung inflammation.
Area of Science:
- Pulmonary toxicology
- Cell biology
- Immunology
Background:
- Multinucleated giant cells (MGC) arise from macrophage fusion in pathological conditions.
- MGC formation is well-studied in biomaterial responses but less so for inhaled inorganic particles.
- Assessing MGC formation in response to diverse lung-deposited particles is crucial.
Purpose of the Study:
- To quantitatively compare in vivo macrophage fusion induced by various micron- and nano-sized particles.
- To investigate MGC formation in response to environmental and engineered inorganic particles in the lungs.
Main Methods:
- C57Bl/6 mice were exposed to crystalline silica, carbon nanotubes, titanium nanobelts, or asbestos.
- Lung cells were collected after one week via lavage for analysis.
- Macrophage fusion, cell differentials, and particle uptake were quantified and observed microscopically.
Main Results:
- MGC were detected in the lungs of all particle-exposed mice, but not in controls.
- Asbestos exposure led to significant MGC formation, increased lavage cells, and elevated neutrophils.
- Microscopy revealed particle internalization in MGC and potential macrophage-neutrophil fusion.
Conclusions:
- MGC can form rapidly in mouse lungs within one week of particle exposure.
- Quantifiable MGC formation suggests it's a significant response, not a rare event.
- Further research into MGC's role in particle clearance and inflammation is warranted.

