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.