FLEROXACIN ENHANCEMENT OF SUPEROXIDE PRODUCTION BY POLYMORPHONUCLEAR LEUKOCYTES - THE ROLE OF PROTEIN-KINASES

New quinolone (NQ) antimicrobials may influence the functions of polym orphonuclear leukocyes (PMNs). Fleroxacin (FLRX), one of the newer NQs which has a long half-life in blood and a strong bactericidal effect, was examined for its influence on superoxide production by PMNs. Augm entation of superoxide production by PMNs when stimulated with phorbol myristate acetate (PMA) and formyl-methionyl-leucyl-phenylalanine (fM LP) was observed following the addition of 25, 50, 100 and 200 mu g/ml of FLRX. In addition, the effects of staurosporine and H-7, inhibitor s of protein kinase C (PKC), and of genistein, a tyrosine kinase (TK) inhibitor, on Fl-RX-enhanced superoxide production were examined. Supe roxide production augmented by FLRX was diminished by the addition of staurosporine and H-7, when PMNs were stimulated with PMA, and by the addition of genistein, when PMNs were stimulated with fMLP. These resu lts suggest that FLRX augments superoxide production by PMNs through e nhancing the activities of phosphorylation by PKC or TK within the sig nal transduction pathway in PMNs.