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Silica particles cause NADPH oxidase–independent ROS generation and transient phagolysosomal leakage

Chronic inhalation of silica particles causes lung fibrosis and silicosis. Silica taken up by alveolar macrophages causes phagolysosomal membrane damage and leakage of lysosomal material into the cytoplasm to initiate apoptosis. We investigated the role of reactive oxygen species (ROS) in this membr...

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Autores principales: Joshi, Gaurav N., Goetjen, Alexandra M., Knecht, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569308/
https://www.ncbi.nlm.nih.gov/pubmed/26202463
http://dx.doi.org/10.1091/mbc.E15-03-0126
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author Joshi, Gaurav N.
Goetjen, Alexandra M.
Knecht, David A.
author_facet Joshi, Gaurav N.
Goetjen, Alexandra M.
Knecht, David A.
author_sort Joshi, Gaurav N.
collection PubMed
description Chronic inhalation of silica particles causes lung fibrosis and silicosis. Silica taken up by alveolar macrophages causes phagolysosomal membrane damage and leakage of lysosomal material into the cytoplasm to initiate apoptosis. We investigated the role of reactive oxygen species (ROS) in this membrane damage by studying the spatiotemporal generation of ROS. In macrophages, ROS generated by NADPH oxidase 2 (NOX2) was detected in phagolysosomes containing either silica particles or nontoxic latex particles. ROS was only detected in the cytoplasm of cells treated with silica and appeared in parallel with an increase in phagosomal ROS, as well as several hours later associated with mitochondrial production of ROS late in apoptosis. Pharmacological inhibition of NOX activity did not prevent silica-induced phagolysosomal leakage but delayed it. In Cos7 cells, which do not express NOX2, ROS was detected in silica-containing phagolysosomes that leaked. ROS was not detected in phagolysosomes containing latex particles. Leakage of silica-containing phagolysosomes in both cell types was transient, and after resealing of the membrane, endolysosomal fusion continued. These results demonstrate that silica particles can generate phagosomal ROS independent of NOX activity, and we propose that this silica-generated ROS can cause phagolysosomal leakage to initiate apoptosis.
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spelling pubmed-45693082015-11-30 Silica particles cause NADPH oxidase–independent ROS generation and transient phagolysosomal leakage Joshi, Gaurav N. Goetjen, Alexandra M. Knecht, David A. Mol Biol Cell Articles Chronic inhalation of silica particles causes lung fibrosis and silicosis. Silica taken up by alveolar macrophages causes phagolysosomal membrane damage and leakage of lysosomal material into the cytoplasm to initiate apoptosis. We investigated the role of reactive oxygen species (ROS) in this membrane damage by studying the spatiotemporal generation of ROS. In macrophages, ROS generated by NADPH oxidase 2 (NOX2) was detected in phagolysosomes containing either silica particles or nontoxic latex particles. ROS was only detected in the cytoplasm of cells treated with silica and appeared in parallel with an increase in phagosomal ROS, as well as several hours later associated with mitochondrial production of ROS late in apoptosis. Pharmacological inhibition of NOX activity did not prevent silica-induced phagolysosomal leakage but delayed it. In Cos7 cells, which do not express NOX2, ROS was detected in silica-containing phagolysosomes that leaked. ROS was not detected in phagolysosomes containing latex particles. Leakage of silica-containing phagolysosomes in both cell types was transient, and after resealing of the membrane, endolysosomal fusion continued. These results demonstrate that silica particles can generate phagosomal ROS independent of NOX activity, and we propose that this silica-generated ROS can cause phagolysosomal leakage to initiate apoptosis. The American Society for Cell Biology 2015-09-15 /pmc/articles/PMC4569308/ /pubmed/26202463 http://dx.doi.org/10.1091/mbc.E15-03-0126 Text en © 2015 Joshi et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Joshi, Gaurav N.
Goetjen, Alexandra M.
Knecht, David A.
Silica particles cause NADPH oxidase–independent ROS generation and transient phagolysosomal leakage
title Silica particles cause NADPH oxidase–independent ROS generation and transient phagolysosomal leakage
title_full Silica particles cause NADPH oxidase–independent ROS generation and transient phagolysosomal leakage
title_fullStr Silica particles cause NADPH oxidase–independent ROS generation and transient phagolysosomal leakage
title_full_unstemmed Silica particles cause NADPH oxidase–independent ROS generation and transient phagolysosomal leakage
title_short Silica particles cause NADPH oxidase–independent ROS generation and transient phagolysosomal leakage
title_sort silica particles cause nadph oxidase–independent ros generation and transient phagolysosomal leakage
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569308/
https://www.ncbi.nlm.nih.gov/pubmed/26202463
http://dx.doi.org/10.1091/mbc.E15-03-0126
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AT knechtdavida silicaparticlescausenadphoxidaseindependentrosgenerationandtransientphagolysosomalleakage