Lipid peroxidation and ceroid accumulation in macrophages cultured with oxidized low density lipoprotein

When mouse peritoneal macrophages were cultured with oxidized human low density lipoprotein (ox-LDL), storage of ceroid-like pigments was observed within the cells by light and fluorescent microscopy, and fluorescence spectrophotometry. The fluorescent products exhibit the characteristics of Schiff base structures, having a fluorescence maximum of 430 nm and an excitation maximum of 355 nm, which has been generally accepted with fluorescent lipid peroxidation products. Similar fluorescent products were isolated from the atherosclerotic lesions of the aged human artery. Ox-LDL was also intraperitoneally injected into guinea pigs to study an early stage of ceroid accumulation in macrophages. An early event in guinea pigs was the appearance of neutrophils. The findings from the model systems suggest that the ox-LDL in the artery wall is probable chemotactic for neutrophils as well as monocytes. We propose the hypothesis that the production of superoxide by neutrophils causes further lipid peroxidation of native LDL and then produces large amounts of oxidatively modified LDL which is the souse of ceroid pigment accumulated within the foam cells in human atherosclerotic lesions.