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Updated: Mar 13, 2026
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker
Line S Bisgaard1,2, Christina K Mogensen2, Alexander Rosendahl2,3
1Dept. of Biomedical Sciences, University of Copenhagen, Denmark.
Abstract:
Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE-/- mice, their M1/M2 phenotype, inflammatory status, and lipid metabolism signatures were compared. oxLDL accumulation was similar in PEMs and BMDMs. On protein expression level, BMDMs showed an M2-like CD206highCD11clow profile, while cholesterol loading led to enhanced CD11c expression and reduced MCP-1 secretion. In contrast, PEMs expressed low levels of CD206 and CD11c, and responded to cholesterol loading by increasing CD11c expression and MCP-1 secretion. mRNA expression of M1/M2 markers was higher in PEMS than BMDMs, while lipid metabolism genes were similarly expressed. Whole aorta flow cytometry showed an accumulation of M2-like CD206highCD11clow macrophages in advanced versus early atherosclerotic disease in ApoE-/- mice. In isolated lesions, mRNA levels of the M2 markers Socs2, CD206, Retnla, and IL4 were downregulated with increasing disease severity. Likewise, mRNA expression of lipid metabolism genes (SREBP2, ACSL1, SRB1, DGAT1, and cpt1a) was decreased in advanced versus early lesions. In conclusion, PEMs and BMDMs are phenotypically distinct and differ from macrophages in lesions with respect to expression of M1/M2 markers and lipid metabolism genes.
Insights
Peritoneal macrophages (PEMs) and bone marrow-derived macrophages (BMDMs) exhibit distinct phenotypes and differ from aortic macrophages in atherosclerosis. Their inflammatory and lipid profiles vary, impacting their roles in disease progression.
Area of Science:
- Immunology
- Cardiovascular Research
- Cell Biology
Background:
- Macrophages are key immune cells with diverse phenotypes, including pro-inflammatory (M1-like) and remodeling (M2-like) subsets.
- Understanding macrophage heterogeneity is crucial for studying inflammatory diseases like atherosclerosis.
Purpose of the Study:
- To compare the M1/M2 phenotype, inflammatory status, and lipid metabolism of peritoneal macrophages (PEMs) and bone marrow-derived macrophages (BMDMs).
- To determine if PEMs or BMDMs resemble aortic macrophages found in ApoE-/- mice with atherosclerosis.
Main Methods:
- Protein and mRNA expression analysis of M1/M2 markers and lipid metabolism genes.
- Flow cytometry on whole aortas and isolated lesions from ApoE-/- mice.
- Cholesterol loading experiments on PEMs and BMDMs.
Main Results:
- BMDMs displayed an M2-like profile (CD206highCD11c low), while PEMs showed low CD206 and CD11c expression.
- Cholesterol loading increased CD11c and decreased MCP-1 secretion in BMDMs, but increased CD11c and MCP-1 secretion in PEMs.
- Aortic macrophages in advanced atherosclerosis showed an M2-like phenotype, with decreased M2 markers and lipid metabolism gene expression in advanced lesions.
Conclusions:
- PEMs and BMDMs are phenotypically distinct and do not fully recapitulate the characteristics of macrophages within atherosclerotic lesions.
- Macrophage phenotype and function within atherosclerotic lesions change with disease severity, showing a shift away from M2-like markers and lipid metabolism genes in advanced stages.
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