TY - JOUR
T1 - Extracellular vesicles released by microglia and macrophages carry endocannabinoids which foster oligodendrocyte differentiation
AU - Lombardi, Marta
AU - Scaroni, Federica
AU - Gabrielli, Martina
AU - Raffaele, Stefano
AU - Bonfanti, Elisabetta
AU - Filipello, Fabia
AU - Giussani, Paola
AU - Picciolini, Silvia
AU - de Rosbo, Nicole Kerlero
AU - Uccelli, Antonio
AU - Golia, Maria Teresa
AU - D'Arrigo, Giulia
AU - Rubino, Tiziana
AU - Hooshmand, Kourosh
AU - Legido-Quigley, Cristina
AU - Fenoglio, Chiara
AU - Gualerzi, Alice
AU - Fumagalli, Marta
AU - Verderio, Claudia
N1 - Copyright © 2024 Lombardi, Scaroni, Gabrielli, Raffaele, Bonfanti, Filipello, Giussani, Picciolini, de Rosbo, Uccelli, Golia, D’Arrigo, Rubino, Hooshmand, Legido-Quigley, Fenoglio, Gualerzi, Fumagalli and Verderio.
PY - 2024/2/23
Y1 - 2024/2/23
N2 - 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.
AB - 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.
KW - 2-arachidonoylglycerol
KW - anandamide
KW - endocannabinoids
KW - extracellular vesicles
KW - macrophages
KW - microglia
KW - oligodendrocytes
UR - http://www.scopus.com/inward/record.url?scp=85186871837&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2024.1331210
DO - 10.3389/fimmu.2024.1331210
M3 - Journal article
C2 - 38464529
SN - 1664-3224
VL - 15
SP - 1331210
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1331210
ER -