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Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages

Microglia (MG) and macrophages (MPs) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and...

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Autores principales: Zhang, Ian, Alizadeh, Darya, Liang, Junling, Zhang, Leying, Gao, Hang, Song, Yanyan, Ren, Hui, Ouyang, Mao, Wu, Xiwei, D’Apuzzo, Massimo, Badie, Behnam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147798/
https://www.ncbi.nlm.nih.gov/pubmed/27936099
http://dx.doi.org/10.1371/journal.pone.0165118
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author Zhang, Ian
Alizadeh, Darya
Liang, Junling
Zhang, Leying
Gao, Hang
Song, Yanyan
Ren, Hui
Ouyang, Mao
Wu, Xiwei
D’Apuzzo, Massimo
Badie, Behnam
author_facet Zhang, Ian
Alizadeh, Darya
Liang, Junling
Zhang, Leying
Gao, Hang
Song, Yanyan
Ren, Hui
Ouyang, Mao
Wu, Xiwei
D’Apuzzo, Massimo
Badie, Behnam
author_sort Zhang, Ian
collection PubMed
description Microglia (MG) and macrophages (MPs) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and anti-inflammatory functions dictates their antitumor activity. To evaluate potential variations in MG and MP function in gliomas, we isolated these cells (and other Gr1(+) cells) from intracranial GL261 murine gliomas by FACS and evaluated their gene expression profiles by microarray analysis. As expected, arginase 1 (Arg1, M2 marker) was highly expressed by tumor-associated Gr1(+), MG and MP. However, in contrast to MP and Gr1(+) cells that expressed Arg1 shortly after tumor trafficking, Arg1 expression in MG was delayed and occurred in larger tumors. Interestingly, depletion of MPs in tumors did not prevent MG polarization, suggesting direct influence of tumor-specific factors on MG Arg1 upregulation. Finally, Arg1 expression was confirmed in human GBM samples, but most Arg1(+) cells were neutrophils and not MPs. These findings confirm variations in tumor MG and MP polarization states and its dependency on tumor microenvironmental factors.
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spelling pubmed-51477982016-12-28 Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages Zhang, Ian Alizadeh, Darya Liang, Junling Zhang, Leying Gao, Hang Song, Yanyan Ren, Hui Ouyang, Mao Wu, Xiwei D’Apuzzo, Massimo Badie, Behnam PLoS One Research Article Microglia (MG) and macrophages (MPs) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and anti-inflammatory functions dictates their antitumor activity. To evaluate potential variations in MG and MP function in gliomas, we isolated these cells (and other Gr1(+) cells) from intracranial GL261 murine gliomas by FACS and evaluated their gene expression profiles by microarray analysis. As expected, arginase 1 (Arg1, M2 marker) was highly expressed by tumor-associated Gr1(+), MG and MP. However, in contrast to MP and Gr1(+) cells that expressed Arg1 shortly after tumor trafficking, Arg1 expression in MG was delayed and occurred in larger tumors. Interestingly, depletion of MPs in tumors did not prevent MG polarization, suggesting direct influence of tumor-specific factors on MG Arg1 upregulation. Finally, Arg1 expression was confirmed in human GBM samples, but most Arg1(+) cells were neutrophils and not MPs. These findings confirm variations in tumor MG and MP polarization states and its dependency on tumor microenvironmental factors. Public Library of Science 2016-12-09 /pmc/articles/PMC5147798/ /pubmed/27936099 http://dx.doi.org/10.1371/journal.pone.0165118 Text en © 2016 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhang, Ian
Alizadeh, Darya
Liang, Junling
Zhang, Leying
Gao, Hang
Song, Yanyan
Ren, Hui
Ouyang, Mao
Wu, Xiwei
D’Apuzzo, Massimo
Badie, Behnam
Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages
title Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages
title_full Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages
title_fullStr Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages
title_full_unstemmed Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages
title_short Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages
title_sort characterization of arginase expression in glioma-associated microglia and macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147798/
https://www.ncbi.nlm.nih.gov/pubmed/27936099
http://dx.doi.org/10.1371/journal.pone.0165118
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