Effects of grepafloxacin on the function of human polymorphonuclear leukocytes and the phosphorylation of p38 mitogen-activated protein kinase.
BACKGROUND
Some new quinolones (NQs) modulate polymorphonuclear leukocyte (PMN) functions. We investigated these effects on PMN functions at concentrations <10 microg/ml.


METHODS
Chemotactic activity and the production of reactive oxygen species (ROS) were measured using a 48-well chemotaxis chamber and by luminol-dependent chemiluminescence (CL) activity, respectively. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) was measured by Western blot using specific antibodies to its phosphorylation sites.


RESULTS
Grepafloxacin (GPFX) at concentrations >5 microg/ml increased the chemotactic activity and ROS production of PMNs after stimulation with N-formylmethionyl-leucyl-phenylalanine (fMLP), whereas prulifloxacin (PUFX) showed no effect. In contrast to PUFX, GPFX at concentrations >1 microg/ml stimulated the phosphorylation of p38 MAPK.


CONCLUSIONS
GPFX enhanced the chemotactic activity and ROS production of PMNs after stimulation with fMLP at concentrations <10 microg/ml. These effects of GPFX on PMNs could be in part due to the enhancement of p38 MAPK phosphorylation.
Koshio
Osamu
O
Department of Microbiology and Immunology, Teikyo University School of Medicine, Tokyo, Japan. koshio@med.teikyo-u.ac.jp
Ono
Yasuo
Y
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004148:Dioxolanes / Q000494:pharmacology; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D004148:Dioxolanes; D024841:Fluoroquinolones; D010879:Piperazines; D017382:Reactive Oxygen Species; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C074191:prulifloxacin; C075375:grepafloxacin