Phospholipase A2 and phospholipase D are involved in macrophage NADPH oxidase-mediated oxidation of low density lipoprotein.

Macrophage-mediated oxidation of low density lipoprotein (LDL) under oxidative stress induces activation of reduced nicotinamide adenine dinuleotide phosphate (NADPH) oxidase. Using J-774 A.1 macrophages, the present study demonstrates that phospholipase A2 (PLase A2) as well as phospholipase D (PLase D) are involved in macrophage NADPH oxidase-mediated oxidation of LDL. Furthermore, the products of these phospholipases, arachidonic acid and phosphatidic acid, can induce NADPH oxidase activation, followed by cell-mediated oxidation of LDL. This LDL oxidation was shown to be dependent on extracellular calcium ions. We conclude that PLase A2 and PLase D can induce macrophage NADPH oxidase-dependent oxidation of LDL and thus can contribute to the formation of atherogenic oxidized lipoprotein.