THE EFFECTS OF FREE-RADICAL SCAVENGERS ON THE OXIDATION OF LOW-DENSITY LIPOPROTEINS BY MACROPHAGES

Oxidised LDL has been implicated in the pathogenesis of atherosclerosi s. Macrophages can oxidatively modify low-density lipoprotein (LDL) in vitro. The mechanisms of this oxidation process are presently unclear . In this study, we have investigated the effects of compounds and enz ymes widely used to quench or scavenge active oxygen species to try to identify the oxidative species involved in this process. The data obt ained suggest that hydrogen peroxide may possibly play a role in LDL o xidation by macrophages, whereas singlet oxygen and hydroxyl radicals may not. The role of superoxide anions was uncertain because copper-zi nc superoxide dismutase (Cu/Zn-SOD) and manganese SOD (Mn-SOD), widely used to determine superoxide-dependency in other systems may be unsui table in this particular system. Cu/Zn-SOD at high concentrations disp layed a variability in its effects, sometimes augmenting LDL oxidation and sometimes inhibiting it. In the experiments in which Cu/Zn-SOD au gmented LDL oxidation, heat inactivation of the enzyme decreased the a ugmentation; in the experiments in which Cu/Zn-SOD inhibited LDL oxida tion, it retained its inhibitory effect after heat inactivation. Mn-SO D always inhibited modification even after heat inactivation. We have therefore concluded that superoxide involvement in LDL oxidation by ma crophages is still uncertain and the uncertainty will remain until a s uitable probe is found.