Adenosine induces histamine release from human bronchoalveolar lavage mastcells

Previous studies have shown that in vitro adenosine enhances histamine rele ase from activated human lung mast cells obtained by enzymic dispersion of lung parenchyma. However, adenosine alone has no effect on histamine releas e from these cells. Given the evidence for direct activation of mast cells after endobronchial challenge with adenosine and previous studies indicatin g that mast cells obtained at bronchoalveolar lavage are a better model for asthma studies than those obtained by enzymic dispersion of lung tissue, t he histamine-releasing effect of adenosine was examined on lavage mast cell s. Bronchoalveolar lavage fluid was obtained from patients attending hospit al for routine bronchoscopy (n = 54). Lavage cells were challenged with ade nosine or adenosine receptor agonists (20 min, 37 degrees C) and histamine release determined using an automated fluorometric assay. Endogenous adenos ine levels were also measured in lavage fluid (n = 9) via an HPLC method. A denosine alone caused histamine release from ravage mast cells in 37 of 54 patients with a maximal histamine release of 20.56 +/- 2.52% (range 5.2-61 %). The adenosine receptor agonists (R)-N-6-(2-phenylisopropyl)adenosine, 5 '-N-ethylcarboxamido-adenosine and CGS21680 also induced histamine release from lavage mast cells. Preincubation of lavage mast cells with the adenosi ne receptor antagonist xanthine amine congener caused significant inhibitio n of the response to adenosine (P = 0.007). There was an inverse correlatio n between endogenous adenosine levels in the lavage fluid and the maximal r esponse to in vitro adenosine challenge of the lavage cells. The findings o f the present study indicate a means by which adenosine challenge of the ai rways can induce bronchoconstriction and support a role for adenosine in th e pathophysiology of asthma. The results also suggest that cells obtained f rom bronchoalveolar ravage fluid may provide the ideal model for the testin g of novel, adenosine receptor, targeted therapies for asthma.