Open AccessMicrovesicles carrying LRP5 induce macrophage polarization to an anti‐inflammatory phenotype
Author(s) -
Luquero Aureli,
Vilahur Gemma,
Crespo Javier,
Badimon Lina,
BorrellPages Maria
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16723
Subject(s) - microbiology and biotechnology , microvesicles , macrophage polarization , lrp5 , macrophage , cd16 , biology , wnt signaling pathway , inflammation , microvesicle , chemistry , immunology , signal transduction , microrna , biochemistry , immune system , in vitro , gene , cd3 , cd8
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.