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Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Myeloperoxidase-Oxidized LDLs Enhance an Anti-Inflammatory M2 and Antioxidant Phenotype in Murine Macrophages
Valérie Pireaux1, Aude Sauvage1, Benoît Bihin2
1URBC-Narilis, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium.
Abstract:
Macrophages and oxidized LDLs play a key role in atherogenesis but their heterogeneity has been neglected up to now. Macrophages are prone to polarization and subsets of polarized macrophages have been described in atheromas. LDLs can be oxidized not only chemically by copper (Ox-LDLs) but also enzymatically by myeloperoxidase (MpOx-LDLs) resulting in oxidized LDLs poor in lipid peroxides. The effects of physiologically relevant myeloperoxidase-oxidized LDLs on macrophage polarization or on polarized macrophages remain largely unknown. In this study, the effects of LDLs on macrophage polarization were investigated by monitoring the expression of M1 and M2 genes following stimulation with native LDLs, Ox-LDLs, or MpOx-LDLs in RAW 264.7 cells. Except for MRC1, which is induced only by Ox-LDLs, MpOx-LDLs induced an overexpression of most of the selected marker genes at the mRNA level. MpOx-LDLs also modulate marker gene expression in polarized macrophages favoring notably anti-inflammatory Arg1 expression in M2 cells and also in the other phenotypes. Noteworthy, MpOx-LDLs were the most efficient to accumulate lipids intracellularly in (un)polarized macrophages whatever the phenotype. These data were largely confirmed in murine bone marrow-derived macrophages. Our data suggest that MpOx-LDLs were the most efficient to accumulate within cells and to enhance an anti-inflammatory and antioxidant phenotype in M2 cells and also in the other macrophage phenotypes.
Insights
Myeloperoxidase-oxidized LDLs (MpOx-LDLs) significantly impact macrophage polarization and lipid accumulation. MpOx-LDLs promote an anti-inflammatory phenotype in various macrophage subsets, influencing atherogenesis research.
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Macrophages and oxidized low-density lipoproteins (LDLs) are crucial in atherogenesis.
- Macrophage polarization and LDL oxidation heterogeneity are understudied in this process.
- Myeloperoxidase-oxidized LDLs (MpOx-LDLs) differ from chemically oxidized LDLs (Ox-LDLs).
Purpose of the Study:
- To investigate the effects of native LDLs, Ox-LDLs, and MpOx-LDLs on macrophage polarization.
- To determine how MpOx-LDLs influence gene expression in polarized and unpolarized macrophages.
- To assess the lipid accumulation capacity of different LDL types in macrophages.
Main Methods:
- RAW 264.7 cells and murine bone marrow-derived macrophages were stimulated with native LDLs, Ox-LDLs, or MpOx-LDLs.
- Macrophage polarization was assessed by monitoring M1 and M2 marker gene expression at the mRNA level.
- Intracellular lipid accumulation was quantified in treated macrophages.
Main Results:
- MpOx-LDLs induced overexpression of most M1 and M2 marker genes, unlike Ox-LDLs which primarily induced MRC1.
- MpOx-LDLs modulated gene expression in polarized macrophages, favoring anti-inflammatory Arg1 expression.
- MpOx-LDLs were most efficient in causing intracellular lipid accumulation across all macrophage phenotypes.
Conclusions:
- Myeloperoxidase-oxidized LDLs are potent modulators of macrophage polarization and lipid metabolism.
- MpOx-LDLs promote an anti-inflammatory and antioxidant phenotype in macrophages, influencing atherogenesis.
- These findings highlight the distinct biological effects of different LDL oxidation states on macrophage function.
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