Abstract
Grepafloxacin is an asymmetric fluoroquinolone derivative, which possesses high tissue penetrability as well as strong, broad-spectrum antimicrobial activities. Human neutrophils actively internalize fluoroquinolones, especially grepafloxacin, and grepafloxacin induces a priming effect on neutrophil respiratory burst produced by fMLP. However the precise mechanism of the uptake and the priming effect are not fully understood. We show here that mitogen activated protein kinase (MAPK) plays a role in the uptake and in the priming effect in neutrophils. Our results strongly suggest that grepafloxacin negatively regulates its uptake in neutrophils, and p38 MAPK activation is involved in this down-regulation of grepafloxacin uptake. The ciprofloxacin uptake is positively regulated by the activation of PKC, and p44/42 MAPK activation is involved in this up-regulation. Neither PKC, nor p38 or p44/42 MAPK is involved in the regulation of ofloxacin uptake. Grepafloxacin stereospecifically primes neutrophil respiratory burst. Stereospecific phosphorylation of p38MAPK, and translocation of p47 and p67 phox proteins are closely related to grepafloxacin priming.
