Inhibitory effect of a synthetic protease inhibitor (gabexate mesilate) on the respiratory burst oxidase in human neutrophils.
We investigated the mechanism by which the synthetic protease inhibitor gabexate mesilate inhibits the production of the superoxide anion by human neutrophils. We found that gabexate mesilate suppressed SOD-inhibitable cytochrome c reduction in a dose-dependent manner in intact neutrophils activated with phorbol ester. Gabexate mesilate slightly scavenged the superoxide anion in the pyrogallol assay. The reagent also inhibited superoxide anion production in a dose-dependent manner in a cell-free oxidase-activating system. Translocation of the cytosolic respiratory burst oxidase components, the 47- and 65-kDa proteins, to membranes was suppressed by the reagent in intact cells stimulated with phorbol ester. Gabexate mesilate also reduced arachidonic acid-induced translocation of the components to the membrane fraction in the cell-free system. These results demonstrate that gabexate mesilate suppresses superoxide anion production by reducing the translocation of the 47- and 65-kDa proteins to the plasma membrane.
Ohashi
I
I
Department of Surgery II, Osaka University Medical School.
Nishijima
J
J
Murata
A
A
Toda
H
H
Kato
T
T
D002462:Cell Membrane / Q000187:drug effects; D002474:Cell-Free System; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D016670:Gabexate / Q000494:pharmacology*; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000187:drug effects*; D019255:NADPH Oxidases; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects; D010084:Oxidation-Reduction; D012016:Reference Values; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015842:Serine Proteinase Inhibitors; D013481:Superoxides; D016670:Gabexate; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C022709:superoxide-forming enzyme; D013755:Tetradecanoylphorbol Acetate