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 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 degrees 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 beta-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.
Kopprasch
S
S
Department of Internal Medicine III, Carl Gustav Carus Medical School, Technical University of Dresden, Germany.
Leonhardt
W
W
Pietzsch
J
J
Kühne
H
H
D002448:Cell Adhesion; D015550:Cell Degranulation; D003300:Copper / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000494:pharmacology*; D008163:Luminescent Measurements; D009113:Muramidase / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014471:Umbilical Veins
D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D013481:Superoxides; D003571:Cytochalasin B; D006997:Hypochlorous Acid; D003300:Copper; D006861:Hydrogen Peroxide; D009113:Muramidase; D005966:Glucuronidase