Myeloid cell subpopulations compensate each other for Ccr2-deficiency in glioblastoma.
Ccr2−/− transgenic mice
GBM
chimera
macrophages
microglia
Journal
Neuropathology and applied neurobiology
ISSN: 1365-2990
Titre abrégé: Neuropathol Appl Neurobiol
Pays: England
ID NLM: 7609829
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
revised:
07
08
2022
received:
13
11
2021
accepted:
09
10
2022
pubmed:
9
11
2022
medline:
3
3
2023
entrez:
8
11
2022
Statut:
ppublish
Résumé
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 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. 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. 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.
Substances chimiques
Ccr2 protein, mouse
0
Receptors, CCR2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12863Subventions
Organisme : Bundesministerium für Bildung und Forschung
Organisme : Deutsche Forschungsgemeinschaft
Organisme : Berliner Krebsgesellschaft
Organisme : Charité - Universitätsmedizin Berlin
Organisme : Sonnenfeld foundation
Organisme : German Federal Ministry of Education and Research
ID : 01EW1811
Organisme : German Research Foundation
ID : SPP1190
Informations de copyright
© 2022 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.
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