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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| Veröffentlicht in: | PloS one 2011-08, Vol.6 (8), p.e23902-e23902 |
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| creator | Gabrusiewicz, Konrad Ellert-Miklaszewska, Aleksandra Lipko, Maciej Sielska, Malgorzata Frankowska, Marta Kaminska, Bozena |
| 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. |
| doi_str_mv | 10.1371/journal.pone.0023902 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0023902</identifier><identifier>PMID: 21901144</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accumulation ; Angiogenesis ; Animal tissues ; Animals ; Biochemical characteristics ; Biochemistry ; Biology ; Brain ; Brain - metabolism ; Brain cancer ; Brain tumors ; Cancer therapies ; CD11b antigen ; CD11b Antigen - metabolism ; Cell activation ; Cell Line, Tumor ; Cells, Cultured ; Cerebrospinal fluid ; Chemokines ; Chemokines, CXC - metabolism ; Chemotherapy ; Cyclosporins ; Cytokines ; Cytometry ; Cytotoxicity ; Dendritic cells ; Extracellular matrix ; Flow Cytometry ; Fluorescent Antibody Technique ; Gene expression ; Genes ; Genetic aspects ; Genotype & phenotype ; Glioma ; Glioma - metabolism ; Glioma - pathology ; Glioma cells ; Gliomas ; Granulocyte-macrophage colony-stimulating factor ; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism ; Growth factors ; Histopathology ; Immunofluorescence ; Immunohistochemistry ; Immunosuppression ; Infiltration ; Inflammation ; Inoculation ; Interleukin 10 ; Interleukin-10 - metabolism ; Kinetics ; Laboratories ; Macrophages ; Macrophages - metabolism ; Macrophages - pathology ; Male ; Matrix Metalloproteinase 14 - metabolism ; Matrix Metalloproteinase 2 - metabolism ; Matrix metalloproteinases ; Medicine ; Metastases ; Mice ; Mice, Inbred C57BL ; Microglia ; Microglia - metabolism ; Microglia - pathology ; Penicillin ; Phenotypes ; Proteases ; Studies ; Tumors</subject><ispartof>PloS one, 2011-08, Vol.6 (8), p.e23902-e23902</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Gabrusiewicz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gabrusiewicz, Konrad</au><au>Ellert-Miklaszewska, Aleksandra</au><au>Lipko, Maciej</au><au>Sielska, Malgorzata</au><au>Frankowska, Marta</au><au>Kaminska, Bozena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-08-25</date><risdate>2011</risdate><volume>6</volume><issue>8</issue><spage>e23902</spage><epage>e23902</epage><pages>e23902-e23902</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21901144</pmid><doi>10.1371/journal.pone.0023902</doi><tpages>e23902</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1307896883 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Accumulation Angiogenesis Animal tissues Animals Biochemical characteristics Biochemistry Biology Brain Brain - metabolism Brain cancer Brain tumors Cancer therapies CD11b antigen CD11b Antigen - metabolism Cell activation Cell Line, Tumor Cells, Cultured Cerebrospinal fluid Chemokines Chemokines, CXC - metabolism Chemotherapy Cyclosporins Cytokines Cytometry Cytotoxicity Dendritic cells Extracellular matrix Flow Cytometry Fluorescent Antibody Technique Gene expression Genes Genetic aspects Genotype & phenotype Glioma Glioma - metabolism Glioma - pathology Glioma cells Gliomas Granulocyte-macrophage colony-stimulating factor Granulocyte-Macrophage Colony-Stimulating Factor - metabolism Growth factors Histopathology Immunofluorescence Immunohistochemistry Immunosuppression Infiltration Inflammation Inoculation Interleukin 10 Interleukin-10 - metabolism Kinetics Laboratories Macrophages Macrophages - metabolism Macrophages - pathology Male Matrix Metalloproteinase 14 - metabolism Matrix Metalloproteinase 2 - metabolism Matrix metalloproteinases Medicine Metastases Mice Mice, Inbred C57BL Microglia Microglia - metabolism Microglia - pathology Penicillin Phenotypes Proteases Studies Tumors |
| title | Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-16T00%3A52%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Characteristics%20of%20the%20alternative%20phenotype%20of%20microglia/macrophages%20and%20its%20modulation%20in%20experimental%20gliomas&rft.jtitle=PloS%20one&rft.au=Gabrusiewicz,%20Konrad&rft.date=2011-08-25&rft.volume=6&rft.issue=8&rft.spage=e23902&rft.epage=e23902&rft.pages=e23902-e23902&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0023902&rft_dat=%3Cgale_plos_%3EA476881689%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1307896883&rft_id=info:pmid/21901144&rft_galeid=A476881689&rft_doaj_id=oai_doaj_org_article_51b303dc86ad4a7e9c6fdb31f3259d2e&rfr_iscdi=true |