Oxidative modification of low density lipoproteins by human polymorphonuclear leukocytes

Abstract

Oxidatively modified low density lipoproteins are thought to play an important role in the generation of macrophage-derived foam cells in early atherosclerotic lesions. Cultured endothelial cells, monocytes, macrophages and smooth muscle cells can modify low density lipoproteins, either by a free radical mechanism or by the action of lipoxygenases. Previous studies demonstrated that activated human polymorphonuclear leukocytes can oxidize low density lipoprotein lipids. Stimulation of the cells with phorbol 12-myristate 13-acetate resulted in an increase both in superoxide anion production and in low density lipoprotein oxidation. The present results show that the oxidative modification of low density lipoproteins by human polymorphonuclear leukocytes can be inhibited by superoxide dismutase but not by the lipoxygenase inhibitor, (5,8,11,14)-eicosatetraynoic acid. The low density lipoproteins oxidized by polymorphonuclear leukocytes were recognized by the scavenger receptor of macrophages (P 388 cell line). It is proposed that the superoxide anion is an important factor in the oxidative modification of low density lipoproteins induced by polymorphonuclear leukocytes, and that under conditions of increased oxidative metabolism in vivo, polymorphonuclear leukocytes can contribute to foam cell formation by a scavenger receptor-dependent process at lesion sites.