Inhibition of allergen-induced basophil activation by ASM-024, a nicotinic receptor ligand.
| Autor: | Watson BM; Department of Medicine, McMaster University, Hamilton, Ont., Canada., Oliveria JP, Nusca GM, Smith SG, Beaudin S, Dua B, Watson RM, Assayag EI, Cormier YF, Sehmi R, Gauvreau GM |
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| Jazyk: | angličtina |
| Zdroj: | International archives of allergy and immunology [Int Arch Allergy Immunol] 2014; Vol. 165 (4), pp. 255-64. Date of Electronic Publication: 2015 Feb 05. |
| DOI: | 10.1159/000370068 |
| Abstrakt: | Background: Nicotinic acetylcholine receptors (nAChRs) were identified on eosinophils and shown to regulate inflammatory responses, but nAChR expression on basophils has not been explored yet. Objective: We investigated surface receptor expression of nAChR α4, α7 and α1/α3/α5 subunits on basophils. Furthermore, we examined the effects of ASM-024, a synthetic nicotinic ligand, on in vitro anti-IgE and in vivo allergen-induced basophil activation. Methods: Basophils were enriched from the peripheral blood of allergic donors and the expression of nAChR subunits and muscarinic receptors was determined. Purified basophils were stimulated with anti-IgE in the presence of ASM-024 with or without muscarinic or nicotinic antagonists for the measurement of CD203c expression and histamine release. The effect of 9 days of treatment with 50 and 200 mg ASM-024 on basophil CD203c expression was examined in the blood of mild allergic asthmatics before and after allergen inhalation challenge. Results: nAChR α4, α7 and α1/α3/α5 receptor subunit expression was detected on basophils. Stimulation of basophils with anti-IgE increased CD203c expression and histamine release, which was inhibited by ASM-024 (10(-5) to 10(-)(3) M, p < 0.05). The effect of ASM-024 was reversed in the presence of muscarinic and nicotinic antagonists. In subjects with mild asthma, ASM-024 inhalation significantly inhibited basophil CD203c expression measured 24 h after allergen challenge (p = 0.03). Conclusion: This study shows that ASM-024 inhibits IgE- and allergen-induced basophil activation through both nicotinic and muscarinic receptors, and suggests that ASM-024 may be an efficacious agent for modulating allergic asthma responses. (© 2015 S. Karger AG, Basel.) |
| Databáze: | MEDLINE |
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