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 (PMNs), macrophages and lymphocytes. We examined the effects of NQs on superoxide (SO) production of PMNs following stimulation of phorbol myristate acetate (PMA). Ofloxacin (OFLX) and fleroxacin (FLRX) significantly augmented SO production of PMNs compared to lomefloxacin, sparfloxacin. Staurosporin and H-7, specific inhibitors of protein kinase C of SO production pathway in PMNs, inhibited augmented SO production by OFLX and FLRX in the concentration-dependent manner. NADPH oxidase activity was not influenced by OFLX in cell lysate assay system. These results suggest that OFLX and FLRX augmented PMN function through enhancing protein kinase activity, but not through direct enhancement of NADPH oxidase.