Prooxidant and antioxidant activities of macrophages in metal-mediated LDLoxidation - The importance of metal sequestration

Murine macrophages incubated in metal-supplemented RPMI could block or prom ote oxidation of low-density lipoprotein (LDL) depending on the degree of m etal supplementation. Only at high concentrations of Cu (1 mu mol/L) and Fe (30 mu mol/L) were cells prooxidant, leading to an accelerated rate of LDL oxidation over that measured in comparable cell-free media. At lower conce ntrations of Cu and Fe in RPMI, LDL oxidation in the presence of macrophage s was inhibited relative to the cell-free condition. This appeared to be de pendent on a stable modification of the culture medium, because preconditio ning of media by incubation with macrophages could also decrease their capa city to sustain subsequent cell-free LDL oxidation. This was due, in part, to a removal of metal from the media during preconditioning. However, resup plementation of media with metals did not fully restore oxidative capacity, indicating that other cell-dependent antioxidant modifications occurred. T his did not involve significant alterations to the thiol content of the med ia. This study highlights the complexity of the role that cells such as mac rophages have with regards to LDL oxidation in vitro and demonstrate that t here are both antioxidative and prooxidative components.