Fleroxacin enhancement of superoxide production by polymorphonuclear leukocytes: the role of protein kinases.
New quinolone (NQ) antimicrobials may influence the functions of polymorphonuclear 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. Augmentation of superoxide production by PMNs when stimulated with phorbol myristate acetate (PMA) and formyl-methionyl-leucyl-phenylalanine (fMLP) was observed following the addition of 25, 50, 100 and 200 micrograms/ml of FLRX. In addition, the effects of staurosporine and H-7, inhibitors of protein kinase C (PKC), and of genistein, a tyrosine kinase (TK) inhibitor, on FLRX-enhanced superoxide production were examined. Superoxide 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 results suggest that FLRX augments superoxide production by PMNs through enhancing the activities of phosphorylation by PKC or TK within the signal transduction pathway in PMNs.
Matsumoto
T
T
Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Takahashi
K
K
Nagafuji
T
T
Kubo
S
S
Sakumoto
M
M
Mochida
O
O
Sakamoto
Y
Y
Mizunoe
Y
Y
Kumazawa
J
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016576:Fleroxacin / Q000494:pharmacology*; D019833:Genistein; D006801:Humans; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology; D011494:Protein Kinases / Q000097:blood / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000890:Anti-Infective Agents; D002273:Carcinogens; D004791:Enzyme Inhibitors; D007529:Isoflavones; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019833:Genistein; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D016576:Fleroxacin; D013755:Tetradecanoylphorbol Acetate