Oxidation of Low-Density Lipoprotein by Human Monocyte-Macrophages Results in Toxicity to the Oxidising Culture

Abstract

Human monocyte-macrophage cultures were exposed to native low density lipoprotein (LDL) for up to 24 h in Ham's F10 medium and the extent of cell-mediated LDL oxidation was determined by measurement of electrophoretic mobility on agarose gels and measurement of lipids and oxidised lipids (including 7β-hydroxycholesterol) by GC. After an initial lag phase, which varied from 2–8 h, there was a steady increase in oxidation over 24 h. No-cell control incubations showed minimal increases in oxidation over 24 h. Significant toxicity, measured as release of radioactivity from macrophages pre-loaded with tritiated adenine, was observed in the cells when they oxidised LDL and the extent of radioactivity release correlated closely with the extent of LDL oxidation. Inhibition of oxidation using α-tocopherol or probucol reduced toxicity within the oxidising culture. This self-inflicted toxicity may help to explain the origin and enlargement of the lipid core of advanced atherosclerotic lesions.

Key Words:

• Low density lipoprotein
• Oxidation
• Monocyte-macrophages (human)
• Cytotoxicity
• Antioxidants
• Atherosclerosis