title: Disparity in FcεRI-induced degranulation of primary human lung and skin mast cells exposed to adenosine.
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 G(i)-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.
authors: Department of Internal Medicine, Virginia Commonwealth University, Box 980263, Richmond, VA 23298, USA. gvgomez@vcu.edu
authors: Gregorio
authors: G
authors: Gomez
authors: Wei
authors: W
authors: Zhao
authors: Lawrence B
authors: LB
authors: Schwartz
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D058909:Adenosine A3 Receptor Agonists / Q000494:pharmacology; D058918:Adenosine A3 Receptor Antagonists / Q000494:pharmacology; D001249:Asthma / Q000276:immunology / Q000473:pathology; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D043684:Receptor, Adenosine A3 / Q000235:genetics / Q000378:metabolism*; D017455:Receptors, IgE / Q000737:chemistry* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D058909:Adenosine A3 Receptor Agonists; D058918:Adenosine A3 Receptor Antagonists; D016085:Bronchoconstrictor Agents; C543355:FcepsilonRI alpha-chain, human; D012333:RNA, Messenger; D043684:Receptor, Adenosine A3; D017455:Receptors, IgE; D000241:Adenosine