Inhaled tryptase causes bronchoconstriction in sheep via histamine release

Area of Science:

• Allergy and Immunology
• Pulmonary Medicine
• Pharmacology

Background:

• Allergen-induced bronchoconstriction is linked to mast cell activation.
• Tryptase, a mast cell protease, is released during allergic reactions.
• The role of tryptase in airway function remains largely unknown.

Purpose of the Study:

• To investigate if aerosolized tryptase induces bronchoconstriction.
• To elucidate the mechanism behind tryptase-mediated airway effects.
• To assess tryptase's role in airway hyperresponsiveness.

Main Methods:

• Allergic sheep were challenged with aerosolized tryptase (100 and 500 ng).
• Pulmonary flow resistance (RL) was measured before and after challenges.
• Studies were repeated after pretreatment with a tryptase inhibitor (APC 366) or histamine H1-antagonist (chlorpheniramine).
• Histamine levels in bronchoalveolar lavage fluid were analyzed.
• Airway hyperresponsiveness to carbachol was assessed post-tryptase challenge.

Main Results:

• Inhaled tryptase significantly increased pulmonary flow resistance in a dose-dependent manner.
• Tryptase-induced bronchoconstriction was blocked by the specific tryptase inhibitor APC 366.
• The response was also inhibited by the histamine H1-antagonist chlorpheniramine.
• Tryptase challenge led to increased histamine levels in bronchoalveolar lavage fluid.
• Inhaled tryptase induced airway hyperresponsiveness, which could be blocked by APC 366.

Conclusions:

• Inhaled tryptase causes significant bronchoconstriction in allergic sheep.
• Tryptase-induced airway effects are mediated, at least in part, by histamine release.
• Tryptase plays a role in the development of airway hyperresponsiveness.
• Mast cell activation appears to be a key event in tryptase-mediated airway responses.