Involvement of endotoxins or tumor necrosis factor-alpha in macrophage-mediated oxidation of low density lipoprotein.

Oxidation of low-density lipoprotein (LDL) can be mediated in vitro by cultured cells, including macrophages. This cellular oxidation is dependent on the production of free thiols by the cells in the presence of transition metal ions. We now report that the production of thiols by macrophages is greatly enhanced when cells are cultured with lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha). Oxidation of LDL by macrophages is markedly augmented by pre-treatment of the cells with LPS or TNF-alpha. The results suggest that activation by endotoxins or TNF-alpha is a necessary step for macrophages to mediate oxidation of LDL.