转录组
趋化因子
清道夫受体
巨噬细胞
CD36
生物
细胞生物学
单核细胞
基因表达
四氯化碳
川地163
三氯化碳
免疫系统
巨噬细胞集落刺激因子
CXCL10型
CCL22型
受体
免疫学
基因
脂蛋白
胆固醇
生物化学
体外
作者
Christian A. Gleissner,Iftach Shaked,Kristina M. Little,Klaus Ley
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2010-05-01
卷期号:184 (9): 4810-4818
被引量:242
标识
DOI:10.4049/jimmunol.0901368
摘要
In atherosclerotic arteries, blood monocytes differentiate to macrophages in the presence of growth factors, such as macrophage colony-stimulation factor (M-CSF), and chemokines, such as platelet factor 4 (CXCL4). To compare the gene expression signature of CXCL4-induced macrophages with M-CSF-induced macrophages or macrophages polarized with IFN-gamma/LPS (M1) or IL-4 (M2), we cultured primary human peripheral blood monocytes for 6 d. mRNA expression was measured by Affymetrix gene chips, and differences were analyzed by local pooled error test, profile of complex functionality, and gene set enrichment analysis. Three hundred seventy-five genes were differentially expressed between M-CSF- and CXCL4-induced macrophages; 206 of them overexpressed in CXCL4 macrophages coding for genes implicated in the inflammatory/immune response, Ag processing and presentation, and lipid metabolism. CXCL4-induced macrophages overexpressed some M1 and M2 genes and the corresponding cytokines at the protein level; however, their transcriptome clustered with neither M1 nor M2 transcriptomes. They almost completely lost the ability to phagocytose zymosan beads. Genes linked to atherosclerosis were not consistently upregulated or downregulated. Scavenger receptors showed lower and cholesterol efflux transporters showed higher expression in CXCL4- than M-CSF-induced macrophages, resulting in lower low-density lipoprotein content. We conclude that CXCL4 induces a unique macrophage transcriptome distinct from known macrophage types, defining a new macrophage differentiation that we propose to call M4.
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