Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression – implications for atherosclerosis research

• Published in: Scientific reports Vol. 6; no. 1; p. 35234
• Main Authors: Bisgaard, Line S., Mogensen, Christina K., Rosendahl, Alexander, Cucak, Helena, Nielsen, Lars Bo, Rasmussen, Salka E., Pedersen, Tanja X.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.10.2016; Nature Publishing Group
• Subjects: 13/31; 38; 64; 64/60; 692/4019/592/75/593; 692/4019/592/75/593/2100; Atherosclerosis; Bone marrow; Humanities and Social Sciences; Immunology; Inflammation; Lipids; Macrophages; Metabolism; multidisciplinary; Rodents; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep35234

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 CD206 high CD11c low 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 CD206 high CD11c low 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.