OXIDATION OF LOW-DENSITY-LIPOPROTEIN BY HUMAN MONOCYTE-MACROPHAGES RESULTS IN TOXICITY TO THE OXIDIZING CULTURE

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 electrop horetic mobility on agarose gels and measurement of lipids and oxidise d lipids (including 7 beta-hydroxycholesterol) by GC. After an initial lag phase, which varied from 2-8 h, there was a steady increase in ox idation over 24 h. No-cell control incubations showed minimal increase s 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 radioa ctivity release correlated closely with the extent of LDL oxidation. I nhibition of oxidation using alpha-tocopherol or probucol reduced toxi city within the oxidising culture. This self-inflicted toxicity may he lp to explain the origin and enlargement of the lipid core of advanced atherosclerotic lesions.