Macrophage fusion caused by particle instillation

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...

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Main Authors: Kevin L. Trout, Andrij Holian
Format: Article
Language:English
Published: Elsevier 2020-06-01
Series:Current Research in Toxicology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666027X20300062
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author Kevin L. Trout
Andrij Holian
author_facet Kevin L. Trout
Andrij Holian
author_sort Kevin L. Trout
collection DOAJ
description 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.
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spelling doaj.art-4da887b13ad343e6b4f161d1532ad63c2022-12-21T21:24:34ZengElsevierCurrent Research in Toxicology2666-027X2020-06-0114247Macrophage fusion caused by particle instillationKevin L. Trout0Andrij Holian1Department of Biomedical and Pharmaceutical Sciences, University of Montana, 32 Campus Dr, Missoula, MT 59812, United StatesCorresponding author.; Department of Biomedical and Pharmaceutical Sciences, University of Montana, 32 Campus Dr, Missoula, MT 59812, United StatesBackground: 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.http://www.sciencedirect.com/science/article/pii/S2666027X20300062Multinucleated giant cellMacrophageCell fusionMouseLungParticles
spellingShingle Kevin L. Trout
Andrij Holian
Macrophage fusion caused by particle instillation
Current Research in Toxicology
Multinucleated giant cell
Macrophage
Cell fusion
Mouse
Lung
Particles
title Macrophage fusion caused by particle instillation
title_full Macrophage fusion caused by particle instillation
title_fullStr Macrophage fusion caused by particle instillation
title_full_unstemmed Macrophage fusion caused by particle instillation
title_short Macrophage fusion caused by particle instillation
title_sort macrophage fusion caused by particle instillation
topic Multinucleated giant cell
Macrophage
Cell fusion
Mouse
Lung
Particles
url http://www.sciencedirect.com/science/article/pii/S2666027X20300062
work_keys_str_mv AT kevinltrout macrophagefusioncausedbyparticleinstillation
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