Effects of polychlorinated biphenyls on the neutrophil NADPH oxidase system.
Polychlorinated biphenyls (PCBs) are reported to induce the formation of reactive oxygen species (ROS) in human neutrophil granulocytes through the activation of the NADPH oxidase. The purpose of the present study is to elucidate the cellular mechanisms responsible for the activation of the NADPH oxidase after exposure to PCB. We have previously shown that PCB activates human neutrophil granulocytes through a calcium dependent activation of phospholipase D and/or phospholipase C, followed by the activation of protein kinase C. In the present study, pharmacological characterization of Aroclor (A) 1242-induced respiratory burst in human neutrophils was conducted by the use of enzymatic inhibitors. Pre-incubation with U0126, SB203580, SP600125, cyclosporin A and FK506 attenuated the A 1242-induced respiratory burst, measured by DCF-fluorescence, and luminol-amplified chemiluminescence. Our results show that the Erk1/2 kinases and p38MAPK/JNK are involved in ROS formation in neutrophils exposed to A 1242.
Myhre
Oddvar
O
Norwegian Defence Research Establishment, Norway. Oddvar.Myhre@ffi.no
Mariussen
Espen
E
Reistad
Trine
T
Voie
Oyvind Albert
OA
Aarnes
Halvor
H
Fonnum
Frode
F
D000873:Anthracenes / Q000494:pharmacology; D001140:Aroclors / Q000633:toxicity*; D002070:Butadienes / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004785:Environmental Pollutants / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008163:Luminescent Measurements; D019255:NADPH Oxidases / Q000097:blood*; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D009570:Nitriles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology
D000873:Anthracenes; D001140:Aroclors; D002070:Butadienes; D004785:Environmental Pollutants; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009570:Nitriles; D011725:Pyridines; C113580:U 0126; C432165:pyrazolanthrone; C027423:aroclor 1242; D016572:Cyclosporine; D019255:NADPH Oxidases; C093642:SB 203580; D016559:Tacrolimus