Inhibitory effects of zafirlukast on respiratory bursts of human neutrophils.
The effects of zafirlukast, a cysteinyl-leukotriene receptor antagonist, on the generation of the reactive oxygen species (ROS) released during respiratory bursts of human polymorphonuclear neutrophils (PMNs) is still unknown. The aim of this study was to investigate the ability of zafirlukast to interfere with the respiratory burst of PMNs. Respiratory burst responses of PMNs were investigated by luminol-amplified chemiluminescence (LACL) using particulate (Candida albicans and zymosan) and soluble stimulants [N-formyl-methionylleucyl-phenylalanine (fMLP) and phorbol 12 myristate 13 acetate (PMA)]. When incubated with PMNs for 10 min at concentrations ranging from 5 x 10(-9) M to 5 x 10(-6) M, zafirlukast did not significantly affect the respiratory bursts of PMNs induced by either the particulate or soluble stimuli. However, after incubation for 60 min, it did reduce the respiratory bursts of PMNs in a concentration-related fashion when the PMNs were stimulated with fMLP, and at a concentration of 5 x 10(-6) M when the stimulus was PMA. No significant effects were seen when the PMNs were challenged with particulate stimuli. Zafirlukast is able to interfere with the activation of the PMNs respiratory burst induced by soluble stimulants. The different behavior determined by different times of contact and different stimuli opens the way to interpretations concerning the antioxidant effect of zafirlukast.
Braga
P C
PC
Center of Respiratory Pharmacology, Department of Pharmacology, School of Medicine, University of Milan, Milan, Italy. bragapc@mailserver.unimi.it
Dal Sasso
M
M
Dal Negro
R
R
D002176:Candida albicans / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D048448:Phenylcarbamates; D016897:Respiratory Burst / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D015054:Zymosan / Q000494:pharmacology
D007211:Indoles; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; D015054:Zymosan; C062735:zafirlukast