MACROPHAGES REQUIRE BOTH IRON AND COPPER TO OXIDIZE LOW-DENSITY-LIPOPROTEIN IN HANKS BALANCED SALT SOLUTION

The oxidation of low-density lipoprotein (LDL) may be important in the pathogenesis of atherosclerosis. However, the interactions between ce lls and metals in promoting LDL oxidation are inadequately understood. A sensitive high-performance Liquid chromatography analysis of choles terol, cholesteryl esters, and their oxidation products was used to id entify and accurately measure LDL oxidation achieved in thiol-free Han ks' balanced salt solution (HBSS) at pH 7.4. Mouse peritoneal macropha ges inhibited LDL oxidation when incubated in HBSS containing either 1 0 mu M iron or 1 mu M copper, but were markedly prooxidant in the pres ence of both metals. The prooxidant effect of macrophages in the prese nce of both iron and copper did not require the provision of added dis ulfides or thiols. Both Fe2+ and macrophages were demonstrated to inde pendently reduce CU2+ to Cu1+ in HBSS, indicating that the direct redu ction of copper by cells or iron may underlie the observed promotion o f LDL oxidation by macrophages in this system. We conclude that macrop hages can either promote or inhibit metal-mediated LDL oxidation and t hat externally supplied thiols are not essential to the promotion of L DL oxidation by cells. The presence of both iron and copper may be par ticularly important for macrophages to promote LDL oxidation in vivo. (C) 1995 Academic Press Inc.