期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：19
页码：10476-10483
DOI：10.1073/pnas.1922879117
出版社：The National Academy of Sciences of the United States of America
摘要：Cholesterol-laden macrophage foam cells are a hallmark of atherosclerosis. For that reason, cholesterol metabolism in macrophages has attracted considerable scrutiny, particularly the mechanisms by which macrophages unload surplus cholesterol (a process referred to as “cholesterol efflux”). Many studies of cholesterol efflux in macrophages have focused on the role of ABC transporters in moving cholesterol onto high-density lipoproteins (HDLs), but other mechanisms for cholesterol efflux likely exist. We hypothesized that macrophages have the capacity to unload cholesterol directly onto adjacent cells. To test this hypothesis, we used methyl-β-cyclodextrin (MβCD) to load mouse peritoneal macrophages with [ 13 C]cholesterol. We then plated the macrophages (in the absence of serum or HDL) onto smooth muscle cells (SMCs) that had been metabolically labeled with [ 15 N]choline. After incubating the cells overnight in the absence of HDL or serum, we visualized 13 C and 15 N distribution by nanoscale secondary ion mass spectrometry (NanoSIMS). We observed substantial 13 C enrichment in SMCs that were adjacent to [ 13 C]cholesterol-loaded macrophages—including in cytosolic lipid droplets of SMCs. In follow-up studies, we depleted “accessible cholesterol” from the plasma membrane of [ 13 C]cholesterol-loaded macrophages with MβCD before plating the macrophages onto the SMCs. After an overnight incubation, we again observed substantial 13 C enrichment in the SMCs adjacent to macrophages. Thus, macrophages transfer cholesterol to adjacent cells in the absence of serum or HDL. We suspect that macrophages within tissues transfer cholesterol to adjacent cells, thereby contributing to the ability to unload surplus cholesterol.
