INHIBITORY EFFECT OF AZELASTINE HYDROCHLORIDE ON SYNTHESIS AND RELEASE OF PLATELET-ACTIVATING-FACTOR FROM HUMAN ALVEOLAR MACROPHAGES

The effect of azelastine hydrochloride (azelastine) on synthesis and r elease of platelet activating factor (PAF) in alveolar macrophages obt ained from asthmatic and non-asthmatic subjects was examined. Alveolar macrophages (AMs) were preincubated with or without azelastine and st imulated with f-Met-Leu-Phe (fMLP, 10 mu M) for 15 min. PAF activity w as detected by aggregation of washed guinea pig platelets. PAF activit y released from alveolar macrophages (AMs) from asthmatics without pre incubation 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-a sthmatic 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 p ellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of azela stine, 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, respective ly. Our results showed that preincubation with azelastine caused a dos e-dependent inhibition of intra-and extracellular PAF activity from as thmatic and non-asthmatic macrophages in the same manner.