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.

Extracellular vesicles released by microglia and macrophages carry endocannabinoids which foster oligodendrocyte differentiation / M. Lombardi, F. Scaroni, M. Gabrielli, S. Raffaele, E. Bonfanti, F. Filipello, P. Giussani, S. Picciolini, N.K. de Rosbo, A. Uccelli, M.T. Golia, G. D’Arrigo, T. Rubino, K. Hooshmand, C. Legido-Quigley, C. Fenoglio, A. Gualerzi, M. Fumagalli, C. Verderio. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 15:(2024 Feb 23), pp. 1331210.1-1331210.14. [10.3389/fimmu.2024.1331210]

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

S. Raffaele;E. Bonfanti;P. Giussani;C. Fenoglio;M. Fumagalli
Penultimo
;
2024

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.
2-arachidonoylglycerol; anandamide; endocannabinoids; extracellular vesicles; macrophages; microglia; oligodendrocytes
Settore BIO/14 - Farmacologia
   Effects of microglia-derived vesicles on GPR17-expressing oligodendrocyte precursors and remyelination after brain ischemia: new molecular insights and recovery potential
   FONDAZIONE CARIPLO
   2015-0910
23-feb-2024
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1331210/full#h11
Article (author)
File in questo prodotto:
File Dimensione Formato  
Lombardi, Scaroni et al., 2024 -Front Immunol.pdf

accesso aperto

Descrizione: Original Research
Tipologia: Publisher's version/PDF
Dimensione 7.19 MB
Formato Adobe PDF
7.19 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1038788
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact