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Modulatory effect of roxithromycin on human neutrophil function
T Mitsuyama1, T Furuno, K Hidaka
1Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abstract:
Neutrophils are thought to play a key role in tissue injury. We investigated the effect of roxithromycin, a 14-membered ring macrolide, on human neutrophil functions. The drug inhibited N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide (O2-) 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 results suggest that the drug affects O2- production and intracellular Ca2+ concentration of neutrophils via the action of PKA. Moreover, roxithromycin ameliorated endothelial cell injury induced by neutrophils, which may be, in part, due to the effect of the drug on neutrophils. Thus, roxithromycin may contribute to the treatment of diseases worsened by the excessive action of neutrophils.
Insights
Roxithromycin, an antibiotic, reduces neutrophil overactivity and protects against tissue injury. This macrolide antibiotic may help treat diseases exacerbated by excessive neutrophil action.
Area of Science:
- Immunology
- Pharmacology
Background:
- Neutrophils are key mediators of tissue injury.
- Understanding neutrophil function modulation is crucial for treating inflammatory diseases.
Purpose of the Study:
- To investigate the effects of roxithromycin on human neutrophil functions.
- To explore the potential of roxithromycin in mitigating neutrophil-induced tissue damage.
Main Methods:
- Human neutrophils were isolated and stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP).
- Superoxide (O2-) production and intracellular calcium (Ca2+) influx were measured.
- The role of cyclic AMP-dependent protein kinase (PKA) was assessed using an inhibitor (H-89).
- Endothelial cell injury models were used to evaluate roxithromycin's protective effects.
Main Results:
- Roxithromycin significantly inhibited fMLP-induced O2- production in neutrophils.
- The drug suppressed fMLP-induced Ca2+ influx in human neutrophils.
- Inhibition of PKA reversed the effects of roxithromycin, suggesting PKA involvement.
- Roxithromycin ameliorated neutrophil-induced endothelial cell injury.
Conclusions:
- Roxithromycin modulates human neutrophil functions, including O2- production and Ca2+ signaling, potentially via PKA.
- Roxithromycin demonstrates protective effects against neutrophil-mediated endothelial cell injury.
- Roxithromycin shows therapeutic potential for conditions involving excessive neutrophil activity.