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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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Detalles Bibliográficos
Autores principales: Trout, Kevin L., Holian, Andrij
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7740110/
https://www.ncbi.nlm.nih.gov/pubmed/33336194
http://dx.doi.org/10.1016/j.crtox.2020.04.003
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author Trout, Kevin L.
Holian, Andrij
author_facet Trout, Kevin L.
Holian, Andrij
author_sort Trout, Kevin L.
collection PubMed
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 pubmed-77401102020-12-16 Macrophage fusion caused by particle instillation Trout, Kevin L. Holian, Andrij Curr Res Toxicol Article 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. Elsevier 2020-05-03 /pmc/articles/PMC7740110/ /pubmed/33336194 http://dx.doi.org/10.1016/j.crtox.2020.04.003 Text en © 2020 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Trout, Kevin L.
Holian, Andrij
Macrophage fusion caused by particle instillation
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7740110/
https://www.ncbi.nlm.nih.gov/pubmed/33336194
http://dx.doi.org/10.1016/j.crtox.2020.04.003
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