title: Inhibitory effects of azelastine hydrochloride on Ca2+ influx, actin polymerization and release of eosinophil cationic protein of an eosinophilic leukaemia cell line EoL-1.
abstract: The inhibitory effects of azelastine hydrochloride on PAF-induced and fMLP-induced Ca2+ influx, actin polymerization and calcium ionophore A23187-induced and aggregated IgG-induced release of eosinophil cationic protein (ECP) of an eosinophilic leukaemia cell line, EoL-1, were examined. EoL-1 cells cultured with 0.2 mM dibutyryladenosine-cyclic monophosphate for 48 hours showed an increase in intracellular free Ca2+ concentration ([Ca2+]i) and actin polymerization when stimulated by PAF and fMLP. Azelastine hydrochloride inhibited PAF-induced and fMLP-induced Ca2+ influx ([Ca2+]i) in a dose-dependent manner with an IC50 of 1 x 10(-8) M and 1 x 10(-7) M, respectively. It also inhibited PAF-induced and fMLP-induced actin polymerization in a dose-dependent manner up to 40% and 30%, respectively. EoL-1 cells were differentiated to contain ECP in their eosinophilic granules when cultured for 9 days with supernatants of a human adult T cell leukaemia cell line, HIL-3 (HIL-3 sup). Calcium ionophore A23187 and aggregated IgG induced the secretion of ECP by EoL-1 cells. Azelastine hydrochloride inhibited the secretion of ECP in a dose-dependent manner. These inhibitory effects were seen even at therapeutic concentrations of 10(-8) M to 10(-9) M. These results indicate that the therapeutic effects of azelastine hydrochloride as an anti-allergic agent may include inhibition of the accumulation of eosinophils into the locus of allergic inflammation and of the release of cytotoxic granules from eosinophils.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Morita
authors.forename: Y
authors.initials: Y
authors.lastname: Ohshima
authors.forename: H
authors.initials: H
authors.lastname: Akutagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Uenoyama
authors.forename: M
authors.initials: M
authors.lastname: Nambu
authors.forename: M
authors.initials: M
authors.lastname: Mayumi
authors.forename: H
authors.initials: H
authors.lastname: Mikawa
mesh_terms: D000199:Actins / Q000187:drug effects*; D001798:Blood Proteins / Q000187:drug effects* / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000187:drug effects*; D002454:Cell Differentiation; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology; D007074:Immunoglobulin G / Q000494:pharmacology; D007249:Inflammation; D015472:Leukemia, Eosinophilic, Acute; D015458:Leukemia, T-Cell; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010793:Phthalazines / Q000494:pharmacology* / Q000627:therapeutic use; D010972:Platelet Activating Factor / Q000494:pharmacology; D011108:Polymers; D012260:Ribonucleases; D014407:Tumor Cells, Cultured
chemical_list: D000199:Actins; D001798:Blood Proteins; D003470:Culture Media; D047091:Eosinophil Granule Proteins; D007074:Immunoglobulin G; D016859:Lipoxygenase Inhibitors; D010793:Phthalazines; D010972:Platelet Activating Factor; D011108:Polymers; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003994:Bucladesine; D012260:Ribonucleases; D000252:Calcium-Transporting ATPases; C020976:azelastine