Effects of staurosporine and genistein on superoxide and HOCl production in C5a- or PMA-activated neutrophils

Abstract

Effects of staurosporine, genistein and pertussis toxin on superoxide and HOCl production in C5a- or PMA-activated neutrophils were investigated. A C5a-induced superoxide and H2O2 production was inhibited by staurosporine, genistein and pertussis toxin. The stimulatory effect of PMA was inhibited by staurosporine but was not affected by pertussis toxin, whereas it was further promoted by genistein. Staurosporine and genistein inhibited superoxide production by sodium fluoride, but pertussis toxin did not affect it. PMA-induced H2O2 production was inhibited by staurosporine but was not affected by pertussis toxin. Genistein did not show a stimulatory effect on PMA-induced H2O2 production. Staurosporine and pertussis toxin inhibited HOCl production by C5a- or PMA, whereas genistein stimulated it. C5a- or PMA-induced myeloperoxidase release was inhibited by genistein, in this response the effect of pertussis toxin was not detected. Staurosporine did not affect the stimulatory effect of PMA on the release. Myeloperoxidase activity was markedly increased by genistein but was not affected by staurosporine and pertussis toxin. These results indicate that the respiratory burst of neutrophils may be regulated by protein kinase C and protein tyrosine kinase. Superoxide production induced by the direct activation of protein kinase C might be affected by protein tyrosine kinase oppositely. Genistein probably promotes HOCl production by activating myeloperoxidase.