Mast Cell Tryptase Causes Airway Smooth Muscle

Supernatants obtained by degranulation of dog mastocytoma cells greatly increased the sensitivity and the magnitude of the contractile response of isolated dog bronchial smooth muscle to histamine. The enhanced contractile response was reversed completely by Hi-receptor antagonists and was prevented by an inhibitor of tryptase (a major protease released with histamine from secretory granules of mast cells). The potentiation of histamine-induced contractions was reproduced by active tryptase in pure form. The contractions due to the combination of histamine and purified tryptase were abolished by the (a2+ channel blockers nifedipine and verapamil. The bronchoconstricting effects of KCI and serotonin, which, like histamine, contract airway smooth muscle by a mechanism predominantly involving membrane potential-dependent Ca2+ transport, were also potentiated by tryptase. However, the contractile effects of acetylcholine, which contracts dog airway smooth muscle by a mechanism independent of Ca2` channels, were unaffected by tryptase. These findings show a striking promotion of agonistinduced bronchial smooth muscle contraction by mast cell tryptase, via direct or indirect effects on (a2+ channels, and the findings therefore suggest a novel potential mechanism of hyperresponsiveness in dog bronchi.