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 inhibito r gabexate mesilate inhibits the production of the superoxide anion by human neutrophils. We found that gabexate mesilate suppressed SOD-inh ibitable cytochrome c reduction in a dose-dependent manner in intact n eutrophils activated with phorbol ester. Gabexate mesilate slightly sc avenged 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 r espiratory burst oxidase components, the 47- and 65-kDa proteins, to m embranes was suppressed by the reagent in intact cells stimulated with phorbol ester, Gabexate mesilate also reduced arachidonic acid-induce d translocation of the components to the membrane fraction in the cell -free system. These results demonstrate that gabexate mesilate suppres ses superoxide anion production by reducing the translocation of the 4 7- and 65-kDa proteins to the plasma membrane.