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Myeloid cell subpopulations compensate each other for Ccr2-deficiency in glioblastoma.
Bungert, Alexander D; Urbantat, Ruth M; Jelgersma, Claudius; Bekele, Biniam M; Mueller, Susanne; Mueller, Annett; Felsenstein, Matthäus; Dusatko, Silke; Blank, Anne; Ghori, Adnan; Boehm-Sturm, Philipp; Koch, Stefan P; Vajkoczy, Peter; Brandenburg, Susan.
Afiliação
  • Bungert AD; Department of Experimental Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Urbantat RM; Department of Experimental Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Jelgersma C; Department of Experimental Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Bekele BM; Department of Experimental Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Mueller S; Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Mueller A; Center for Stroke Research Berlin, Berlin, Germany.
  • Felsenstein M; Department of Experimental Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Dusatko S; Department of Experimental Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Blank A; Department of Experimental Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Ghori A; Department of Experimental Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Boehm-Sturm P; Department of Experimental Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Koch SP; Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Vajkoczy P; Center for Stroke Research Berlin, Berlin, Germany.
  • Brandenburg S; Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Neuropathol Appl Neurobiol ; 49(1): e12863, 2023 Feb.
Article em En | MEDLINE | ID: mdl-36346010
ABSTRACT

AIMS:

Glioblastomas are high-grade brain tumours that are characterised by the accumulation of brain-resident microglia and peripheral macrophages. Recruitment of these myeloid cells can be facilitated by CCR2/CCL2 signalling. Besides the well-known CCR2+ macrophages, we have identified microglia expressing CCR2 in glioma tissues. Thus, we investigated how Ccr2-deficiency of one of the myeloid cell populations affects the other population and tumour biology.

METHODS:

We generated four chimeric groups to analyse single and combined Ccr2-deficiency of microglia and macrophages. On day 21 after tumour cell implantation (GL261), we conducted flow cytometry, immunofluorescence and real-time polymerase chain reaction analyses. Tumour volume and metabolism were determined by magnetic resonance imaging and magnetic resonance spectroscopy. Moreover, in vitro studies were performed with primary microglia and bone marrow-derived macrophages.

RESULTS:

We demonstrated reduced infiltration of macrophages and microglia depending on the lack of Ccr2. However, the total number of myeloid cells remained constant except for the animals with dual Ccr2-knockout. Both microglia and macrophages with Ccr2-deficiency showed impaired expression of proinflammatory molecules and altered phagocytic activity. Despite the altered immunologic phenotype caused by Ccr2-deficiency, glioma progression and metabolism were hardly affected. Alterations were detected solely in apoptosis and proliferation of tumours from animals with specific Ccr2-deficient microglia, whereas vessel stability was increased in mice with Ccr2-knockout in both cell populations.

CONCLUSION:

These results indicate that microglia and macrophages provide a homoeostatic balance within glioma tissue and compensate for the lack of the corresponding counterpart. Moreover, we identified that the CCR2/CCL2 axis is involved in the immunologic function of microglia and macrophages beyond its relevance for migration.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glioblastoma / Glioma Limite: Animals Idioma: En Revista: Neuropathol Appl Neurobiol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glioblastoma / Glioma Limite: Animals Idioma: En Revista: Neuropathol Appl Neurobiol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Alemanha