open access publication

Article, 2024

Extracellular vesicles released by microglia and macrophages carry endocannabinoids which foster oligodendrocyte differentiation

FRONTIERS IN IMMUNOLOGY, ISSN 1664-3224, 1664-3224, Volume 15, 10.3389/fimmu.2024.1331210

Contributors

Lombardi, Marta [1] [2] Scaroni, Federica [1] Gabrielli, Martina [1] [2] Raffaele, Stefano [3] Bonfanti, Elisabetta [3] Filipello, Fabia [4] [5] Giussani, Paola [3] Picciolini, Silvia [6] de Rosbo, Nicole Kerlero [7] [8] [9] Uccelli, Antonio [9] [10] Golia, Maria Teresa [1] [2] D'Arrigo, Giulia [1] [2] Rubino, Tiziana [11] Hooshmand, Kourosh [12] Legido-Quigley, Cristina [12] [13] [14] Fenoglio, Chiara [3] [15] Gualerzi, Alice [6] Fumagalli, Marta [3] Verderio, Claudia (Corresponding author) [1] [2]

Affiliations

  1. [1] Natl Res Council CNR, Dept Biomed Sci, Inst Neurosci, Vedano Al Lambro, Italy
    2. [NORA names: Italy; Europe, EU; OECD];
  2. [2] Univ Milano Bicocca, NeuroMi Milan Ctr Neurosci, Milan, Italy
    3. [NORA names: Italy; Europe, EU; OECD];
  3. [3] Univ Milan, Dept Biomed Surg & Dent Sci, Milan, Italy
    4. [NORA names: Italy; Europe, EU; OECD];
  4. [4] Sci Inst Res Hospitalizat & Healthcare IRCCS Human, Rozzano, Italy
    5. [NORA names: Italy; Europe, EU; OECD];
  5. [5] Washington Univ St Louis, Dept Psychiat, St Louis, MO USA
    6. [NORA names: United States; America, North; OECD];

Abstract

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.

Keywords

2-arachidonoylglycerol, anandamide, endocannabinoids, extracellular vesicles, macrophages, microglia, oligodendrocytes

Data Provider: Clarivate

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