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A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials

BACKGROUND: The most common causes of granulomatous inflammation are persistent pathogens and poorly-degradable irritating materials. A characteristic pathological reaction to intratracheal instillation, pharyngeal aspiration, or inhalation of carbon nanotubes is formation of epithelioid granulomas...

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Autores principales: Sanchez, Vanesa C, Weston, Paula, Yan, Aihui, Hurt, Robert H, Kane, Agnes B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120675/
https://www.ncbi.nlm.nih.gov/pubmed/21592387
http://dx.doi.org/10.1186/1743-8977-8-17
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author Sanchez, Vanesa C
Weston, Paula
Yan, Aihui
Hurt, Robert H
Kane, Agnes B
author_facet Sanchez, Vanesa C
Weston, Paula
Yan, Aihui
Hurt, Robert H
Kane, Agnes B
author_sort Sanchez, Vanesa C
collection PubMed
description BACKGROUND: The most common causes of granulomatous inflammation are persistent pathogens and poorly-degradable irritating materials. A characteristic pathological reaction to intratracheal instillation, pharyngeal aspiration, or inhalation of carbon nanotubes is formation of epithelioid granulomas accompanied by interstitial fibrosis in the lungs. In the mesothelium, a similar response is induced by high aspect ratio nanomaterials, including asbestos fibers, following intraperitoneal injection. This asbestos-like behaviour of some engineered nanomaterials is a concern for their potential adverse health effects in the lungs and mesothelium. We hypothesize that high aspect ratio nanomaterials will induce epithelioid granulomas in nonadherent macrophages in 3D cultures. RESULTS: Carbon black particles (Printex 90) and crocidolite asbestos fibers were used as well-characterized reference materials and compared with three commercial samples of multiwalled carbon nanotubes (MWCNTs). Doses were identified in 2D and 3D cultures in order to minimize acute toxicity and to reflect realistic occupational exposures in humans and in previous inhalation studies in rodents. Under serum-free conditions, exposure of nonadherent primary murine bone marrow-derived macrophages to 0.5 μg/ml (0.38 μg/cm(2)) of crocidolite asbestos fibers or MWCNTs, but not carbon black, induced macrophage differentiation into epithelioid cells and formation of stable aggregates with the characteristic morphology of granulomas. Formation of multinucleated giant cells was also induced by asbestos fibers or MWCNTs in this 3D in vitro model. After 7-14 days, macrophages exposed to high aspect ratio nanomaterials co-expressed proinflammatory (M1) as well as profibrotic (M2) phenotypic markers. CONCLUSIONS: Induction of epithelioid granulomas appears to correlate with high aspect ratio and complex 3D structure of carbon nanotubes, not with their iron content or surface area. This model offers a time- and cost-effective platform to evaluate the potential of engineered high aspect ratio nanomaterials, including carbon nanotubes, nanofibers, nanorods and metallic nanowires, to induce granulomas following inhalation.
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spelling pubmed-31206752011-06-23 A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials Sanchez, Vanesa C Weston, Paula Yan, Aihui Hurt, Robert H Kane, Agnes B Part Fibre Toxicol Research BACKGROUND: The most common causes of granulomatous inflammation are persistent pathogens and poorly-degradable irritating materials. A characteristic pathological reaction to intratracheal instillation, pharyngeal aspiration, or inhalation of carbon nanotubes is formation of epithelioid granulomas accompanied by interstitial fibrosis in the lungs. In the mesothelium, a similar response is induced by high aspect ratio nanomaterials, including asbestos fibers, following intraperitoneal injection. This asbestos-like behaviour of some engineered nanomaterials is a concern for their potential adverse health effects in the lungs and mesothelium. We hypothesize that high aspect ratio nanomaterials will induce epithelioid granulomas in nonadherent macrophages in 3D cultures. RESULTS: Carbon black particles (Printex 90) and crocidolite asbestos fibers were used as well-characterized reference materials and compared with three commercial samples of multiwalled carbon nanotubes (MWCNTs). Doses were identified in 2D and 3D cultures in order to minimize acute toxicity and to reflect realistic occupational exposures in humans and in previous inhalation studies in rodents. Under serum-free conditions, exposure of nonadherent primary murine bone marrow-derived macrophages to 0.5 μg/ml (0.38 μg/cm(2)) of crocidolite asbestos fibers or MWCNTs, but not carbon black, induced macrophage differentiation into epithelioid cells and formation of stable aggregates with the characteristic morphology of granulomas. Formation of multinucleated giant cells was also induced by asbestos fibers or MWCNTs in this 3D in vitro model. After 7-14 days, macrophages exposed to high aspect ratio nanomaterials co-expressed proinflammatory (M1) as well as profibrotic (M2) phenotypic markers. CONCLUSIONS: Induction of epithelioid granulomas appears to correlate with high aspect ratio and complex 3D structure of carbon nanotubes, not with their iron content or surface area. This model offers a time- and cost-effective platform to evaluate the potential of engineered high aspect ratio nanomaterials, including carbon nanotubes, nanofibers, nanorods and metallic nanowires, to induce granulomas following inhalation. BioMed Central 2011-05-18 /pmc/articles/PMC3120675/ /pubmed/21592387 http://dx.doi.org/10.1186/1743-8977-8-17 Text en Copyright ©2011 Sanchez et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Sanchez, Vanesa C
Weston, Paula
Yan, Aihui
Hurt, Robert H
Kane, Agnes B
A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials
title A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials
title_full A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials
title_fullStr A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials
title_full_unstemmed A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials
title_short A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials
title_sort 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120675/
https://www.ncbi.nlm.nih.gov/pubmed/21592387
http://dx.doi.org/10.1186/1743-8977-8-17
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