Azelastine hydrochloride inhibits platelet activating factor-like activity in human eosinophils.
We investigated the inhibitory effect of azelastine hydrochloride (azelastine), an anti-asthmatic drug, on platelet-activating factor (PAF)-like activity in eosinophils obtained from asthmatic and non-asthmatic patients. Eosinophils were preincubated with or without azelastine and stimulated with f-Met-Leu-Phe (fMLP, 10 mumol) for 15 min. PAF-like activity was detected by aggregation of washed guinea-pig platelets. PAF-like activity released from asthmatic eosinophils without preincubation of azelastine was 2.36 [1.02] (mean [SD], ng/10(7) cells) in supernatants and 13.87 [4.77] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M azelastine, PAF-like activity reduced to 1.85 [0.46] (mean [SD], ng/10(7) cells), 1.11 [0.14], and 0.88 [0.09] (n = 15) in the supernatants, and 11.83 [2.93], 8.32 [1.41], and 6.27 [1.25] (n = 15) in the cell pellets, respectively. PAF-like activity in non-asthmatic eosinophils without preincubation of azelastine was 2.01 [0.86] (mean [SD], ng/10(7) cells) in supernatants and 7.44 [0.99] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M azelastine, PAF-like activity reduced to 1.73 [0.64] (mean [SD], ng/10(7) cells), 1.12 [0.23], and 0.84 [0.17] (n = 20) in the supernatants, and 6.26 [2.08], 4.65 [0.88], and 3.02 [0.43] (n = 20) in the cell pellets, respectively. Our results showed that preincubation with azelastine caused a dose-dependent inhibition of intra and extracellular PAF-like activity from asthmatic and non-asthmatic eosinophils in the same manner.
Shindo
K
K
First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Fukumura
M
M
D000818:Animals; D001249:Asthma / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects*; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010793:Phthalazines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000032:analysis*; D010974:Platelet Aggregation / Q000187:drug effects
D006634:Histamine H1 Antagonists; D010793:Phthalazines; D010972:Platelet Activating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; C020976:azelastine