Inhibition of chemiluminescence in granulocytes and alveolar macrophages by azelastine.
The effect of azelastine, an orally effective antiasthmatic antiallergic drug on the generation of oxygen-derived free radicals in phagocytes was investigated using different chemiluminescence-assays. The chemiluminescence (CL) of both human polymorphonuclear granulocytes (PMNL) and guinea-pig alveolar macrophages (AM) was induced either by phorbol myristate acetate (PMA) or zymosan and amplified either by lucigenin or DMNH (7-dimethylamino-naphthalene-1,2-dicarbonic-acidhydrazide). The inhibitory effect of azelastine was dependent on the inducer employed and the condition and type of cells used. Azelastine reduced PMA-induced CL concentration-dependently in both PMNL (IC30 = 3.9 microM) and AM (IC30 = 9.8 microM). In AM zymosan-induced CL was inhibited 21.7% by 10 microM azelastine, whereas in PMNL it remained unchanged up to 10 microM azelastine. Azelastine has a significantly stronger inhibitory effect (IC30 = 4.2 microM) on oxygen free radical generation in AM primed by fetal calf serum than in unprimed AM. Based on present results it is likely that azelastine inhibits oxygen-derived free radical generation by interaction with protein kinase C.
Schmidt
J
J
Department of Pharmacology, ASTA Pharma AG, Frankfurt, FRG.
Kaufmann
B
B
Lindstaedt
R
R
Szelenyi
I
I
D000166:Acridines / Q000494:pharmacology; D000328:Adult; D000818:Animals; D005456:Fluorescent Dyes; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D007700:Kinetics; D008163:Luminescent Measurements; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D010793:Phthalazines / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D000166:Acridines; D005456:Fluorescent Dyes; D006834:Hydrazines; D009281:Naphthalenes; D010793:Phthalazines; C033472:10,10'-dimethyl-9,9'-biacridinium; C045681:7-dimethylaminonaphthalene-1,2-dicarbonic acid hydrazide; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate; C020976:azelastine