Hypochlorite-modified low-density lipoprotein stimulates human polymorphonuclear leukocytes for enhanced production of reactive oxygen metabolites, enzyme secretion, and adhesion to endothelial cells

Abstract

Hypochlorite-oxidized low-density lipoprotein ( −OCl-LDL) has been shown to stimulate various functions of human polymorphonuclear leukocytes (PMNLs). Incubation of PMNLs with −OCl-LDL (produced by incubation of 0.4 mM LDL cholesterol with 1 mM NaOCl for 40 min at 37°C) but not native or copper-oxidized LDL induced a substantial generation of reactive oxygen species (ROS) as measured by means of chemiluminescence with one peak at 10–12 min. Upon stimulation with −OCl-LDL about 70% of ROS (hydrogen peroxide and superoxide anion) were released from the cells into the extracellular environment. The −OCl-LDL-induced increase of the respiratory burst was dependent upon the dose, exposure time, and extent of LDL oxidation. Cytochalasin B, an inhibitor of phagocytosis, markedly diminished the LDL-induced ROS generation to nearly 40% of control values. −OCl-LDL enhanced the adhesion of PMNLs to human umbilical venous endothelial cells 2.5-fold as compared to native LDL and promoted the secretion of the active granule enzymes lysozyme and β-glucuronidase. Together, the results suggest a potential role of LDL-activated PMNLs in initiating and/or maintaining the inflammatory process during the early phase of atherosclerotic lesion development. Alternatively, PMNLs may also play a protective role by phagocytosing oxidized LDL and, thus, preventing further detrimental atherogenic effects of oxidized LDL.