Okadaic acid inhibits the signal responsible for activation of the NADPH-oxidase in neutrophils stimulated with serum-opsonized yeast.
The effects of the phosphatase inhibitor okadaic acid (OA) on human neutrophil phagocytic activity were investigated. The chemiluminescence response was found to be greatly reduced in OA-treated neutrophils during phagocytosis of serum opsonized yeast particles in comparison to control cells. However, the OA-treated neutrophils phagocytosed yeast particles to the same extent as control cells and the engulfment of the prey was accompanied by phagolysosomal formation in both OA-treated and nontreated cells. We thus found that the OA effect was selective in the sense that it inhibits the NADPH-oxidase activity in neutrophils phagocytosing yeast particles but not uptake of the prey or phagolysosomal formation. Based on the fact that the NADPH-oxidase activity induced by the chemoattractant formyl-methionyl-leucyl-phenylalanine was not reduced but elevated in OA-treated neutrophils, we conclude that the state of phosphorylation has no direct effect on the oxidase, but is of importance for the NADPH-oxidase activating signal(s) generated during phagocytosis of the yeast particles.
Harbecke
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O
The Phagocyte Research Laboratory, Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
Lundqvist
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H
Dahlgren
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D000818:Animals; D002459:Cell Fusion; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D019319:Okadaic Acid; D010587:Phagocytosis / Q000187:drug effects*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D017382:Reactive Oxygen Species; D019319:Okadaic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D010749:Phosphoprotein Phosphatases; D013755:Tetradecanoylphorbol Acetate