Effect of azelastine hydrochloride on release and production of platelet activating factor in human neutrophils.
Effect of azelastine hydrochloride (azelastine) on release and production of platelet-activating factor (PAF) in neutrophils obtained from asthmatic and non-asthmatic patients was investigated. Neutrophils were preincubated with or without azelastine and stimulated with f-Met-Leu-Phe (fMLP, 10 microM) for 15 min. PAF-like activity was detected by aggregation of washed guinea pig platelets. PAF-like activity released from asthmatic neutrophils without preincubation of azelastine was 5.67[0.89] (mean[SD], ng/10(7) cells) in supernatants and 21.8[0.76] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of azelastine, PAF-like activity reduced to 5.96[0.97] (mean[SD], ng/10(7) cells), 3.49[0.63], and 1.89[0.09] (n = 15) in the supernatants, and 20.7[0.97], 13.9[0.29], and 8.91 [0.99] (n = 15) in the cell pellets, respectively. PAF-like activity in non-asthmatic neutrophils without preincubation of azelastine was 4.67[0.19] (mean[SD], ng/10(7) cells) in supernatants and 18.5[0.34] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of azelastine, PAF-like activity reduced to 4.39[0.51] (mean[SD], ng/10(7) cells), 2.77[0.22], and 1.75[0.07] (n = 15) in the supernatants, and 17.9[0.54], 10.8[0.25], and 5.97 [0.59] (n = 15) 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 neutrophils in the same manner.
Shindo
K
K
First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Fukumura
M
M
Hirai
Y
Y
Koide
K
K
D001249:Asthma / Q000378:metabolism*; D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D010793:Phthalazines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D010974:Platelet Aggregation
D010793:Phthalazines; D010972:Platelet Activating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; C020976:azelastine