The protective effects of HDL and its constituents against neutrophil respiratory burst activation by hypochlorite-oxidized LDL.
Hypochlorite-oxidized low-density lipoprotein (oxLDL) possesses a substantial proinflammatory potential by modulating respiratory burst activities of polymorphonuclear neutrophils (PMN). As evaluated by luminol-amplified chemiluminescence (CL) incubation of 10(6) PMN/ml with 70 nM oxLDL was followed by substantial induction of neutrophil oxidant (ROS) generation. We evaluated the inhibitory capacity of high-density lipoprotein (HDL) and its lipid and protein constituents against the activating effects of oxLDL. At a HDL or apolipoprotein AI/LDL protein ratio of 1.0, native HDL decreased the respiratory burst activation by 64%, followed by trypsinized HDL (57%) and native apoAI (43%). The inhibitory effects of native HDL did not require prior incubation with PMN or with oxLDL suggesting an instantaneously acting protective mechanism in the minute range. OxLDL modulated ROS production not only of resting PMN but also that of activated PMN, as indicated by a 14-fold increase in FMLP-stimulated CL response and a 50% decrease in zymosan-mediated CL answer. HDL itself did not protect PMN from activation by FMLP and zymosan. However, it clearly reduced effects of oxLDL on FMLP-activation and slightly counteracted the oxLDL-mediated decrease in zymosan-induced ROS generation. Taken together, these findings may offer new insight into atheroprotective mechanisms of HDL.
Kopprasch
Steffi
S
Department of Internal Medicine 3, Pathological Biochemistry, Carl Gustav Carus Medical School, University of Technology, Dresden, Germany. steffi.kopprasch@mailbox.tu-dresden.de
Pietzsch
Jens
J
Graessler
Juergen
J
D016632:Apolipoprotein A-I / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects*; D010084:Oxidation-Reduction / Q000187:drug effects; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D015054:Zymosan / Q000494:pharmacology*
D016632:Apolipoprotein A-I; D002630:Chemotactic Factors; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D020011:Protective Agents; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006997:Hypochlorous Acid; C049813:N-formylmethionyl-leucyl-phenylalanyl-lysine; D015054:Zymosan