Microvesicles carrying LRP5 induce macrophage polarization to an anti-inflammatory phenotype
Luquero, Aureli (Institut d'Investigació Biomèdica Sant Pau)
Vilahur, Gemma (Institut d'Investigació Biomèdica Sant Pau)
Crespo Asensio, Javier (Institut d'Investigació Biomèdica Sant Pau)
Badimon, Lina (Institut d'Investigació Biomèdica Sant Pau)
Borrell-Pages, Maria (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2021
Abstract:	Microvesicles (MV) contribute to cell-to-cell communication through their transported proteins and nucleic acids. MV, released into the extracellular space, exert paracrine regulation by modulating cellular responses after interaction with near and far target cells. MV are released at high concentrations by activated inflammatory cells. Different subtypes of human macrophages have been characterized based on surface epitopes being CD16 macrophages associated with anti-inflammatory phenotypes. We have previously shown that low-density lipoprotein receptor-related protein 5 (LRP5), a member of the LDLR family that participates in lipid homeostasis, is expressed in macrophage CD16 with repair and survival functions. The goal of our study was to characterize the cargo and tentative function of macrophage-derived MV, whether LRP5 is delivered into MV and whether these MV are able to induce inflammatory cell differentiation to a specific CD16 or CD16 phenotype. We show, for the first time, that lipid-loaded macrophages release MV containing LRP5. LDL loading induces increased expression of macrophage pro-inflammatory markers and increased release of MV containing pro-inflammatory markers. Conditioning of fresh macrophages with MV released by Lrp5-silenced macrophages induced the transcription of inflammatory genes and reduced the transcription of anti-inflammatory genes. Thus, MV containing LRP5 induce anti-inflammatory phenotypes in macrophages.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1480 Agència de Gestió d'Ajuts Universitaris i de Recerca SLT006 Ministerio de Economía y Competitividad CB16/11/00411 Instituto de Salud Carlos III FIS2020-01282 Ministerio de Economía y Competitividad RD16/0011/0018 Agencia Estatal de Investigación PID2019-107160RB-I00
Note:	Altres ajuts: Fundación Investigación Cardiovascular-Fundación Jesus Serra
Note:	Altres ajuts: Sociedad Española de Cardiología FEC2019
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Inflammation ; Lipids ; LRP5 ; Macrophages ; MV
Published in:	Journal of Cellular and Molecular Medicine, Vol. 25 Núm. 16 (august 2021) , p. 7935-7947, ISSN 1582-4934

DOI: 10.1111/jcmm.16723
PMID: 34288375

13 p, 1.7 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles