The serine protease inhibitor diisopropylfluorophosphate inhibits neutrophil NADPH-oxidase activity induced by the calcium ionophore ionomycin and serum opsonised yeast particles.
The effect on human neutrophil NADPH-oxidase activity of the serine protease inhibitor diisopropylfluorophosphate (DFP) was investigated. Pretreatment of neutrophils with the protease inhibitor did not affect the release of reactive oxygen species induced by fMLP. However, the intracellular production of reactive oxygen species induced by ionomycin and yeast particles was largely inhibited in DFP treated cells. Production of reactive oxygen species in subcellular fractions was not affected by the protease inhibitor, neither when the plasma membrane nor when the specific granules were used as source for the b cytochrome subunit of the oxidase. This shows that DFP does not affect the assembly of the oxidase or the activity of the assembled complex. We suggest that serine protease activity is of importance for the signal(s) induced by the Ca2+ ionophore and the yeast particles to reach the dormant NADPH oxidase present in the specific granules and phagolysosomes.
Lundqvist
H
H
Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
Dahlgren
C
C
D000328:Adult; D015415:Biomarkers; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D015759:Ionomycin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007476:Ionophores / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007531:Isoflurophate / Q000494:pharmacology*; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D009895:Opsonin Proteins / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D015002:Yeast, Dried / Q000494:pharmacology*
D015415:Biomarkers; D007476:Ionophores; D009895:Opsonin Proteins; D017382:Reactive Oxygen Species; D015842:Serine Proteinase Inhibitors; D013481:Superoxides; D007531:Isoflurophate; D015759:Ionomycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases