Cytotoxicity of oxidized low-density lipoprotein to mouse peritoneal macrophages: an ultrastructural study.
Mouse peritoneal macrophages (MPM) were incubated in culture medium containing low-density lipoprotein (LDL), oxidized LDL (oxLDL), or as controls, for 24 h. Scanning electron microscopy of MPM exposed to oxLDL showed loss of membrane ruffles and extensive plasmalemmal 'blebbing'. Transmission electron microscopy showed changes in up to 50 per cent of the cells, including vacuolation of the rough endoplasmic reticulum and reorganization of heterochromatin in the nuclei, characteristic of apoptosis. These changes were not seen in controls, nor in macrophages exposed to native LDL. Electron-dense crystals were found in the cytoplasm of 1 in 50 of cells exposed to oxLDL. These were found to have a high content of calcium and phosphorus. It is proposed that oxLDL is capable of inducing apoptosis, which might explain the origin of the necrotic base of advanced atherosclerotic plaques.
Reid
V C
VC
Department of Pathology, University of Cambridge, U.K.
Mitchinson
M J
MJ
Skepper
J N
JN
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004577:Electron Probe Microanalysis; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D010084:Oxidation-Reduction
D008077:Lipoproteins, LDL