EFFECT OF AZELASTINE HYDROCHLORIDE ON RELEASE AND PRODUCTION OF PLATELET-ACTIVATING-FACTOR IN HUMAN NEUTROPHILS

Effect of azelastine hydrochloride (azelastine) on release and product ion of platelet-activating factor (PAF) in neutrophils obtained from a sthmatic and non-asthmatic patients was investigated. Neutrophils were preincubated with or without azelastine and stimulated with f-Met-Leu -Phe (fMLP, 10 mu M) for 15 min. PAF-like activity was detected by agg regation of washed guinea pig platelets.PAF-like activity released fro m 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 azel astine, PAF-like activity reduced to 5.96[0.97](mean[SD], ng/10(7) cel ls), 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, resp ectively. PAF-like activity in non-asthmatic neutrophils without prein cubation of azelastine was 4.67[0.19](mean[SD], ng/10(7) cells) in sup ernatants 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 prei ncubation with azelastine caused a dose-dependent inhibition of intra and extracellular PAF-like activity from asthmatic and non-asthmatic n eutrophils in the same manner.