LDL modification by activated polymorphonuclear leukocytes: a cellular model of mild oxidative stress.
The purpose of this study was to determine the most potent activator of the respiratory burst of polymorphonuclear leukocytes (PMN) with respect to the oxidative modification of low density lipoprotein (LDL). Phorbol-12-myristate-13-acetate (PMA), n-formyl-methionyl-leucylphenylalanine (nFMLP), lipopolysaccharide (LPS), and opsonized zymosan (OZ) were tested. The generation of reactive oxygen species by PMN was assayed as superoxide anion production. Oxidative modification of LDL was monitored by thiobarbituric acid reactive substance (TBARS) activity, by conjugated dienes formation at 234nm and by electrophoretic mobility on agarose gel. PMA was the most potent activator of PMN, inducing a 6-fold increase in the superoxide anion production, followed by OZ (3-fold increase). PMA activation also induced the greatest modification of LDL by PMN: 700% increase of conjugated dienes formation, 222% increase of TBARS, and 70% increase in the electrophoretic mobility. The indices of oxidative modification significantly correlated with the superoxide anion generated by different activators. Also, LDL oxidation by PMN was inhibited by superoxide dismutase but not by catalase, methionine, or hydroxyl radical scavengers. Our data indicate that PMNs activated by PMA produce a mildly oxidized form of LDL by a mechanism that appears to involve the superoxide anion.
Scaccini
C
C
Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas 75235-9052.
Jialal
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I
D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000097:blood*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009895:Opsonin Proteins; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D009895:Opsonin Proteins; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate