HYPOCHLORITE-MODIFIED LOW-DENSITY-LIPOPROTEIN STIMULATES HUMAN POLYMORPHONUCLEAR LEUKOCYTES FOR ENHANCED PRODUCTION OF REACTIVE OXYGEN METABOLITES, ENZYME-SECRETION, AND ADHESION TO ENDOTHELIAL-CELLS

Hypochlorite-oxidized low-density lipoprotein (-OCl-LDL) has been show n 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 degrees C) bu t not native or copper-oxidized LDL induced a substantial generation o f reactive oxygen species (ROS) as measured by means of chemiluminesce nce with one peak at 10-12 min. Upon stimulation with -OCl-LDL about 7 0% of ROS (hydrogen peroxide and superoxide anion) were released from the cells into the extracellular environment. The -OCl-LDL-induced inc rease of the respiratory burst was dependent upon the dose, exposure t ime, and extent of LDL oxidation. Cytochalasin B, an inhibitor of phag ocytosis, markedly diminished the LDL-induced ROS generation to nearly 40% of control values. -OCl-LDL enhanced the adhesion of PMNLs to hum an umbilical venous endothelial cells 2.5-fold as compared to native L DL and promoted the secretion of the active granule enzymes lysozyme a nd beta-glucuronidase. Together, the results suggest a potential role of LDL-activated PMNLs in initiating and/or maintaining the inflammato ry process during the early phase of atherosclerotic lesion developmen t. Alternatively, PMNLs may also play a protective role by phagocytosi ng oxidized LDL and, thus, preventing further detrimental atherogenic effects of oxidized LDL. (C) 1998 Elsevier Science Ireland Ltd.