OFLOXACIN AND FLEROXACIN ENHANCE SUPEROXIDE PRODUCTION IN HUMAN POLYMORPHONUCLEAR LEUKOCYTES BY INCREASING PHOSPHORYLATION IN THE SIGNAL-TRANSDUCTION PATHWAY

Many antimicrobial agents including new quinolones (NQs) influence the cellular defense mechanisms such as polymorphonuclear leukocytes (PMN s), macrophages and lymphocytes. We examined the effects of NQs on sup eroxide (SO) production of PMNs following stimulation of phorbol myris tate acetate (PMA). Ofloxacin (OFLX) and fleroxacin (FLRX) significant ly augmented SO production of PMNs compared to lomefloxacin, sparfloxa cin. Staurosporin and H-7, specific inhibitors of protein kinase C of SO production pathway in PMNs, inhibited augmented SO production by OF LX and FLRX in the concentration-dependent manner. NADPH oxidase activ ity was not influenced by OFLX in cell lysate assay system. These resu lts suggest that OFLX and FLRX augmented PMN function through enhancin g protein kinase activity, but not through direct enhancement of NADPH oxidase.