Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas.

Microglia (brain resident macrophages) accumulate in malignant gliomas and instead of initiating the anti-tumor response, they switch to a pro-invasive phenotype, support tumor growth, invasion, angiogenesis and immunosuppression by release of cytokines/chemokines and extracellular matrix proteases....

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Autores principales:	Konrad Gabrusiewicz, Aleksandra Ellert-Miklaszewska, Maciej Lipko, Malgorzata Sielska, Marta Frankowska, Bozena Kaminska
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/51b303dc86ad4a7e9c6fdb31f3259d2e
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spelling	oai:doaj.org-article:51b303dc86ad4a7e9c6fdb31f3259d2e2021-11-18T06:47:14ZCharacteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas.1932-620310.1371/journal.pone.0023902https://doaj.org/article/51b303dc86ad4a7e9c6fdb31f3259d2e2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21901144/?tool=EBIhttps://doaj.org/toc/1932-6203Microglia (brain resident macrophages) accumulate in malignant gliomas and instead of initiating the anti-tumor response, they switch to a pro-invasive phenotype, support tumor growth, invasion, angiogenesis and immunosuppression by release of cytokines/chemokines and extracellular matrix proteases. Using immunofluorescence and flow cytometry, we demonstrate an early accumulation of activated microglia followed by accumulation of macrophages in experimental murine EGFP-GL261 gliomas. Those cells acquire the alternative phenotype, as evidenced by evaluation of the production of ten pro/anti-inflammatory cytokines and expression profiling of 28 genes in magnetically-sorted CD11b(+) cells from tumor tissues. Furthermore, we show that infiltration of implanted gliomas by amoeboid, Iba1-positive cells can be reduced by a systematically injected cyclosporine A (CsA) two or eight days after cell inoculation. The up-regulated levels of IL-10 and GM-CSF, increased expression of genes characteristic for the alternative and pro-invasive phenotype (arg-1, mt1-mmp, cxcl14) in glioma-derived CD11b(+) cells as well as enhanced angiogenesis and tumor growth were reduced in CsA-treated mice. Our findings define for the first time kinetics and biochemical characteristics of glioma-infiltrating microglia/macrophages. Inhibition of the alternative activation of tumor-infiltrating macrophages significantly reduced tumor growth. Thus, blockade of microglia/macrophage infiltration and their pro-invasive functions could be a novel therapeutic strategy in malignant gliomas.Konrad GabrusiewiczAleksandra Ellert-MiklaszewskaMaciej LipkoMalgorzata SielskaMarta FrankowskaBozena KaminskaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23902 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Konrad Gabrusiewicz Aleksandra Ellert-Miklaszewska Maciej Lipko Malgorzata Sielska Marta Frankowska Bozena Kaminska Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas.
description	Microglia (brain resident macrophages) accumulate in malignant gliomas and instead of initiating the anti-tumor response, they switch to a pro-invasive phenotype, support tumor growth, invasion, angiogenesis and immunosuppression by release of cytokines/chemokines and extracellular matrix proteases. Using immunofluorescence and flow cytometry, we demonstrate an early accumulation of activated microglia followed by accumulation of macrophages in experimental murine EGFP-GL261 gliomas. Those cells acquire the alternative phenotype, as evidenced by evaluation of the production of ten pro/anti-inflammatory cytokines and expression profiling of 28 genes in magnetically-sorted CD11b(+) cells from tumor tissues. Furthermore, we show that infiltration of implanted gliomas by amoeboid, Iba1-positive cells can be reduced by a systematically injected cyclosporine A (CsA) two or eight days after cell inoculation. The up-regulated levels of IL-10 and GM-CSF, increased expression of genes characteristic for the alternative and pro-invasive phenotype (arg-1, mt1-mmp, cxcl14) in glioma-derived CD11b(+) cells as well as enhanced angiogenesis and tumor growth were reduced in CsA-treated mice. Our findings define for the first time kinetics and biochemical characteristics of glioma-infiltrating microglia/macrophages. Inhibition of the alternative activation of tumor-infiltrating macrophages significantly reduced tumor growth. Thus, blockade of microglia/macrophage infiltration and their pro-invasive functions could be a novel therapeutic strategy in malignant gliomas.
format	article
author	Konrad Gabrusiewicz Aleksandra Ellert-Miklaszewska Maciej Lipko Malgorzata Sielska Marta Frankowska Bozena Kaminska
author_facet	Konrad Gabrusiewicz Aleksandra Ellert-Miklaszewska Maciej Lipko Malgorzata Sielska Marta Frankowska Bozena Kaminska
author_sort	Konrad Gabrusiewicz
title	Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas.
title_short	Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas.
title_full	Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas.
title_fullStr	Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas.
title_full_unstemmed	Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas.
title_sort	characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/51b303dc86ad4a7e9c6fdb31f3259d2e
work_keys_str_mv	AT konradgabrusiewicz characteristicsofthealternativephenotypeofmicrogliamacrophagesanditsmodulationinexperimentalgliomas AT aleksandraellertmiklaszewska characteristicsofthealternativephenotypeofmicrogliamacrophagesanditsmodulationinexperimentalgliomas AT maciejlipko characteristicsofthealternativephenotypeofmicrogliamacrophagesanditsmodulationinexperimentalgliomas AT malgorzatasielska characteristicsofthealternativephenotypeofmicrogliamacrophagesanditsmodulationinexperimentalgliomas AT martafrankowska characteristicsofthealternativephenotypeofmicrogliamacrophagesanditsmodulationinexperimentalgliomas AT bozenakaminska characteristicsofthealternativephenotypeofmicrogliamacrophagesanditsmodulationinexperimentalgliomas
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Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas.

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