title: Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression - implications for atherosclerosis research.
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 CD206highCD11clowprofile, 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 CD206highCD11clowmacrophages 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.
authors.affiliation: Dept. of Biomedical Sciences, University of Copenhagen, Denmark.|Dept. of Diabetic Complication Biology, Novo Nordisk, Denmark.
authors.forename: Line S
authors.initials: LS
authors.lastname: Bisgaard
authors.affiliation: Dept. of Diabetic Complication Biology, Novo Nordisk, Denmark.
authors.forename: Christina K
authors.initials: CK
authors.lastname: Mogensen
authors.affiliation: Dept. of Diabetic Complication Biology, Novo Nordisk, Denmark.|Dept. of Biopharmaceuticals New Heamophilia, Novo Nordisk, Denmark.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rosendahl
authors.affiliation: Dept. of Diabetic Complication Biology, Novo Nordisk, Denmark.
authors.forename: Helena
authors.initials: H
authors.lastname: Cucak
authors.affiliation: Dept. of Biomedical Sciences, University of Copenhagen, Denmark.|Dept. of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Denmark.
authors.forename: Lars Bo
authors.initials: LB
authors.lastname: Nielsen
authors.affiliation: Dept. of ADME, Novo Nordisk, Denmark.
authors.forename: Salka E
authors.initials: SE
authors.lastname: Rasmussen
authors.affiliation: Dept. of Biomedical Sciences, University of Copenhagen, Denmark.
authors.forename: Tanja X
authors.initials: TX
authors.lastname: Pedersen
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D005260:Female; D007249:Inflammation / Q000473:pathology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein