MODULATORY EFFECT OF ROXITHROMYCIN ON HUMAN NEUTROPHIL FUNCTION

Neutrophils are thought to play a key role in tissue injury. We invest igated the effect of roxithromycin, a 14-membered ring macrolide, on h uman neutrophil functions. The drug inhibited N-formyl-methionyl-leucy l-phenylalanine (fMLP)-induced superoxide (O-2(-)) production and Ca2 influx of human neutrophils. The inhibition was overcome by adding an inhibitor of cyclic AMP-dependent protein kinase (PKA), H-89. These r esults suggest that the drug affects O-2(-) production and intracellul ar Ca2+ concentration of neutrophils via the action of PKA. Moreover, roxithromycin ameliorated endothelial cell injury induced by neutrophi ls, which may be, in part, due to the effect of the drug on neutrophil s. Thus, roxithromycin may contribute to the treatment of diseases wor sened by the excessive action of neutrophils.