RELEASE OF MAST-CELL-DERIVED MEDIATORS AFTER ENDOBRONCHIAL ADENOSINE CHALLENGE IN ASTHMA

Preformed and newly generated mediators released from airway mast cell s may play a role in adenosine-induced bronchoconstriction. To investi gate the possible role of mast-cell-derived mediator release in mediat ing bronchoconstriction induced by adenosine 5'-monophosphate (AMP), w e have examined the fluid obtained by bronchoalveolar lavage for infla mmatory mediators and markers of airway permeability immediately after instillation of AMP directly into an airway segment of 10 asthmatic s ubjects. Eight subjects completed the protocol. When compared with the saline-challenged segment, the response to endobronchial stimulation with AMP was characterized by a prompt reduction in airway caliber par alleled by a significant rise in PGD(2), histamine, and tryptase level s in the ravage fluid. After AMP challenge, the median (range) concent ration for PGD(2) increased from 36 to 205 pg/ml (p = 0.006), for hist amine from 184 to 433 pg/ml (p = 0.018), and for tryptase from 0.30 to 0.54 ng/ml (p = 0.013). In addition, a small but significant rise in albumin levels (from 27.8 to 36.1 mu g/ml; p = 0.031) was detected aft er endobronchial challenge with AMP. These findings indicate that aden osine-induced responses may be initiated by the acute release of mast- cell-derived mediators, including PGD(2), histamine, and tryptase.