title: Inhibitory effect of azelastine hydrochloride on synthesis and release of platelet activating factor from human alveolar macrophages.
abstract: The effect of azelastine hydrochloride (azelastine) on synthesis and release of platelet activating factor (PAF) in alveolar macrophages obtained from asthmatic and non-asthmatic subjects was examined. Alveolar macrophages (AMs) were preincubated with or without azelastine and stimulated with f-Met-Leu-Phe (fMLP, 10 microM) for 15 min. PAF activity was detected by aggregation of washed guinea pig platelets. PAF activity released from alveolar macrophages (AMs) from asthmatics without preincubation of azelastine was 15.97 [2.17] (mean [SD], ng/10(7) cells) in supernatants and 42.52 [10.16] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of azelastine, PAF activity reduced to 10.71 [2.73] (mean [SD], ng/10(7) cells), 7.86 [0.94], and 3.52 [0.31] in the supernatants, and 35.58 [7.37], 21.57 [4.36], and 14.77 [0.99] (n = 15) in the cell pellets, respectively. PAF activity in non-asthmatic subjects without preincubation of azelastine was 8.55 [1.16] (mean [SD], ng/10(7) cells) in supernatants and 32.64 [3.37] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of azelastine, PAF activity reduced to 6.68 [0.78] (mean [SD], ng/10(7) cells), 4.47 [0.51], and 2.97 [0.36] in the supernatants, and 29.53 [3.75], 14.78 [1.95], and 6.16 [0.55] (n = 20) in the cell pellets, respectively. Our results showed that preincubation with azelastine caused a dose-dependent inhibition of intra- and extracellular PAF activity from asthmatic and non-asthmatic macrophages in the same manner.
authors.affiliation: The First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shindo
authors.forename: M
authors.initials: M
authors.lastname: Machida
authors.forename: Y
authors.initials: Y
authors.lastname: Hirai
authors.forename: M
authors.initials: M
authors.lastname: Fukumura
mesh_terms: D000328:Adult; D001249:Asthma / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010793:Phthalazines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000187:drug effects / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
chemical_list: D010793:Phthalazines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; C020976:azelastine