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Effect of ketotifen on human alveolar macrophages
1First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Abstract:
In order to examine the possibility of human alveolar macrophages being an effector site of an antiasthmatic drug, we studied the effect of ketotifen on chemiluminescence and Ca-activated K conductance at single channel level because they are associated with the activation of macrophages. Peak chemiluminescence response, induced by a single concentration of phorbol myristate acetate (0.5 micrograms/ml), was inhibited by 28 +/- 3, 51 +/- 8, and 76 +/- 7% by ketotifen concentrations of 0.02, 0.12, and 0.24 mmol/L, respectively. The inhibition of chemiluminescence by ketotifen concentrations of 0.12 and 0.24 mmol/L was also observed in macrophages stimulated with zymosan activated serum (54 +/- 7 and 80 +/- 6%, respectively). Moreover, ketotifen, 0.24 mmol/L, inhibited Ca-activated K channel currents by 44 +/- 7% (large currents) and 48 +/- 13% (small currents). These results may explain, at least partly, antiasthmatic effects of ketotifen.
Insights
Ketotifen, an antiasthmatic drug, inhibits macrophage activation by reducing chemiluminescence and Ca-activated K channel currents. These findings suggest a potential mechanism for ketotifen
Area of Science:
- Immunopharmacology
- Cellular Physiology
Background:
- Human alveolar macrophages play a role in asthma pathogenesis.
- Understanding drug effects on macrophage activation is crucial for antiasthmatic therapies.
Purpose of the Study:
- To investigate ketotifen's effects on human alveolar macrophage activation.
- To explore ketotifen's potential as an effector site for antiasthmatic action.
Main Methods:
- Studied the impact of ketotifen on macrophage chemiluminescence.
- Analyzed ketotifen's effect on single-channel Ca-activated K conductance.
- Used phorbol myristate acetate and zymosan-activated serum for macrophage stimulation.
Main Results:
- Ketotifen significantly inhibited chemiluminescence induced by phorbol myristate acetate in a dose-dependent manner.
- Ketotifen also reduced chemiluminescence in macrophages stimulated with zymosan-activated serum.
- Ketotifen inhibited both large and small Ca-activated K channel currents.
Conclusions:
- Ketotifen demonstrates inhibitory effects on key macrophage activation pathways.
- These findings provide a cellular basis for ketotifen's antiasthmatic properties.
