Macrophage uptake of cholesterol-containing particles derived from LDL and isolated from atherosclerotic lesions.
A variety of different cholesterol-rich particles with different physical and chemical structures can be isolated from human atherosclerotic lesions. Many of these particles are internalized in an unregulated fashion by macrophages in culture, leading to lipid loading of these cells. However, the in vivo relevance of this uptake is still uncertain. In this overview, we have summarized data obtained primarily in our laboratory on low density lipoprotein (LDL)-like particles (A-LDL) and large cholesterol-rich droplets isolated from human atherosclerotic lesions. Based on our studies, we propose a variety of different mechanisms of uptake. A-LDL can be internalized by the LDL receptor or the scavenger receptor on macrophages in culture; the latter uptake mechanism can lead to lipid loading. In addition, at high concentrations A-LDL can undergo aggregation, possibly due to intermolecular cross-bridging by aldehydes released during oxidation of these particles. The aggregates are subsequently internalized by macrophages by phagocytosis, a process which appears to be independent of the LDL or scavenger receptor. By contrast, arterial smooth muscle cells do not take up these aggregates. Large cholesteryl ester-rich particles isolated from human lesions, and derived from LDL that had been degraded by hydrolytic enzymes in the extracellular space of the arterial wall, or from inclusions released from lysed foam cells, are also internalized via phagocytosis by macrophages in culture. Since some of these particles contain apoliproteins and/or proteins that are ligands for receptors on macrophages, initial receptor-mediated binding may precede and facilitate subsequent phagocytosis in some cases. Uptake of the diverse group of cholesteryl ester-rich particles in plaques can induce lipid loading of macrophages and therefore may lead to further growth of the atherosclerotic plaque.
Hoff
H F
HF
Research Institute, Cleveland Clinic Foundation, Ohio 44195.
O'Neil
J
J
Pepin
J M
JM
Cole
T B
TB
D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D008078:Cholesterol, LDL / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000502:physiology*
D008078:Cholesterol, LDL