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Updated: Jul 1, 2025
Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Extracellular vesicles released by microglia and macrophages carry endocannabinoids which foster oligodendrocyte
Marta Lombardi1,2, Federica Scaroni1, Martina Gabrielli1,2
1Department of Biomedical Sciences, National Research Council (CNR) Institute of Neuroscience, Vedano al Lambro, Italy.
Introduction:
Microglia and macrophages can influence the evolution of myelin lesions through the production of extracellular vesicles (EVs). While microglial EVs promote in vitro differentiation of oligodendrocyte precursor cells (OPCs), whether EVs derived from macrophages aid or limit OPC maturation is unknown.
Methods:
Immunofluorescence analysis for the myelin protein MBP was employed to evaluate the impact of EVs from primary rat macrophages on cultured OPC differentiation. Raman spectroscopy and liquid chromatography-mass spectrometry was used to define the promyelinating lipid components of myelin EVs obtained in vitro and isolated from human plasma.
Results And Discussion:
Here we show that macrophage-derived EVs do not promote OPC differentiation, and those released from macrophages polarized towards an inflammatory state inhibit OPC maturation. However, their lipid cargo promotes OPC maturation in a similar manner to microglial EVs. We identify the promyelinating endocannabinoids anandamide and 2-arachidonoylglycerol in EVs released by both macrophages and microglia in vitro and circulating in human plasma. Analysis of OPC differentiation in the presence of the endocannabinoid receptor antagonists SR141716A and AM630 reveals a key role of vesicular endocannabinoids in OPC maturation. From this study, EV-associated endocannabinoids emerge as important mediators in microglia/macrophage-oligodendrocyte crosstalk, which may be exploited to enhance myelin repair.
Insights
Extracellular vesicles (EVs) from inflammatory macrophages inhibit oligodendrocyte precursor cell (OPC) maturation. However, the lipid cargo within these EVs, specifically endocannabinoids, promotes OPC differentiation, suggesting a novel therapeutic target for myelin repair.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Extracellular vesicles (EVs) from microglia and macrophages influence myelin lesion development.
- Microglial EVs promote oligodendrocyte precursor cell (OPC) differentiation.
- The role of macrophage-derived EVs in OPC maturation is not well understood.
Purpose of the Study:
- To investigate the impact of macrophage-derived EVs on OPC differentiation.
- To identify the components within macrophage EVs that affect OPC maturation.
- To explore the therapeutic potential of EV-associated molecules for myelin repair.
Main Methods:
- Immunofluorescence analysis of myelin basic protein (MBP) in cultured OPCs.
- Raman spectroscopy and liquid chromatography-mass spectrometry to analyze EV lipid cargo.
- Assessment of OPC differentiation in the presence of EV receptor antagonists.
Main Results:
- Macrophage-derived EVs did not promote OPC differentiation; inflammatory macrophage EVs inhibited it.
- The lipid cargo of macrophage EVs, including endocannabinoids anandamide and 2-arachidonoylglycerol, promoted OPC maturation.
- Vesicular endocannabinoids play a crucial role in OPC maturation via receptor-mediated pathways.
Conclusions:
- Macrophage-EVs have a complex role in OPC maturation, with inflammatory EVs being inhibitory.
- EV-associated endocannabinoids are key mediators in microglia/macrophage-oligodendrocyte communication.
- Targeting EV endocannabinoids may offer a strategy to enhance myelin repair in neurological disorders.
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