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Disparity in FcεRI-Induced Degranulation of Primary Human Lung and Skin Mast Cells Exposed to Adenosine

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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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Authors and Affiliations

  1. Department of Internal Medicine, Virginia Commonwealth University, Box 980263, Richmond, VA, 23298, USA

    Gregorio Gomez & Lawrence B. Schwartz

  2. Department of Pediatrics, Virginia Commonwealth University, Richmond, VA, 23298, USA

    Wei Zhao

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  1. Gregorio Gomez
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  2. Wei Zhao
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  3. Lawrence B. Schwartz
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Correspondence to Gregorio Gomez.

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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

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