Abstract
Inhaled and intravenously administered adenosine induces mast cell-mediated (histamine-dependent) bronchospasm in asthmatics without causing urticaria. A differential response to adenosine by human lung and skin mast cells is shown: low concentrations potentiate FcεRI-induced degranulation of human lung mast cells but not that of skin mast cells. Human lung mast cells were found to express ∼3-fold more A3AR messenger RNA (mRNA) than skin mast cells, suggesting the involvement of the Gi-linked A3AR. Indeed, the adenosine-induced potentiation was sensitive to inhibition by pertussis toxin and, furthermore, could be induced with an A3AR-specific agonist. This study reveals a previously unrecognized disparity in the response to adenosine by primary human mast cells from lung and skin that might explain why adenosine induces a pulmonary but not dermatologic allergy-like response in vivo. In addition, we identify the A3AR as a potentiating receptor of FcεRI-induced degranulation, thereby implicating it in the in vivo bronchoconstrictive response to adenosine in asthmatics.
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Acknowledgments
This study was supported by the National Institutes of Health grants KO1HL092581 and Jeffress Memorial Trust grant to G.G. and R01AI20487 and U19AI077435 to L.B.S.
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Gomez, G., Zhao, W. & Schwartz, L.B. Disparity in FcεRI-Induced Degranulation of Primary Human Lung and Skin Mast Cells Exposed to Adenosine. J Clin Immunol 31, 479–487 (2011). https://doi.org/10.1007/s10875-011-9517-7
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DOI: https://doi.org/10.1007/s10875-011-9517-7