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Inhibitory effect of azelastine hydrochloride on synthesis and release of platelet activating factor from human
1The First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.
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.
Insights
Azelastine hydrochloride significantly reduces platelet-activating factor (PAF) synthesis and release in both asthmatic and non-asthmatic macrophages. This study demonstrates azelastine
Area of Science:
- Immunology
- Pharmacology
- Respiratory Medicine
Background:
- Platelet-activating factor (PAF) plays a key role in inflammatory responses, particularly in asthma.
- Alveolar macrophages (AMs) are crucial immune cells in the lungs involved in PAF production.
- Asthma involves heightened inflammatory responses, potentially linked to increased PAF activity.
Purpose of the Study:
- To investigate the effect of azelastine hydrochloride on PAF synthesis and release.
- To compare azelastine's effects on PAF activity in macrophages from asthmatic versus non-asthmatic individuals.
- To determine if azelastine exhibits a dose-dependent inhibition of PAF activity.
Main Methods:
- Alveolar macrophages (AMs) were isolated from asthmatic and non-asthmatic subjects.
- AMs were preincubated with varying concentrations of azelastine (10⁻⁸ to 10⁻⁴ M).
- Cells were stimulated with f-Met-Leu-Phe (fMLP) and PAF activity was measured in supernatants and cell pellets using guinea pig platelet aggregation.
Main Results:
- Azelastine hydrochloride significantly inhibited both intracellular and extracellular PAF activity in a dose-dependent manner.
- The inhibitory effect of azelastine on PAF activity was observed in macrophages from both asthmatic and non-asthmatic subjects.
- PAF activity was reduced in both cell pellets and supernatants following azelastine preincubation.
Conclusions:
- Azelastine hydrochloride effectively inhibits PAF synthesis and release from human alveolar macrophages.
- The findings suggest azelastine may be a beneficial therapeutic agent for managing inflammatory conditions like asthma.
- The drug's mechanism involves reducing PAF production, impacting inflammatory pathways in the airways.