Cough responses to inhaled irritants are enhanced by eosinophil major basic protein in awake mice

A distinct association between airway eosinophilia and chronic cough is well documented. Eosinophil granule-derived cationic proteins, such as major basic protein (MBP), have been shown to activate and enhance the excitability of bronchopulmonary C-fiber sensory nerves, which may then lead to an increase in cough sensitivity. This study was carried out to determine whether cough responses to inhaled irritant gases were altered by delivery of MBP into the airways. An awake mouse moved freely in a recording chamber that was ventilated with a constant flow of air or irritant gas mixture. Cough responses to separate inhalation challenges of sulfur dioxide (SO₂; 300 and 600 ppm) and ammonia (NH₃; 0.1 and 0.2%), each for 5-min duration, were measured daily for 3 days before and for up to 8 days after MBP (10-20 µg) instillation into the trachea. During control, inhalations of SO₂ and NH₃ consistently elicited cough responses in a dose-dependent manner. After MBP treatment, cough responses to both SO₂ and NH₃ increased significantly and progressively and reached peaks 2-3 days after the treatment before returning to control level in 3-7 days. In sharp contrast, cough responses to these irritant gases were not affected by the treatment with the vehicle of MBP. These results suggest that the MBP-induced lingering elevation of cough responsiveness may be a contributing factor in the pathogenesis of chronic cough associated with eosinophilic infiltration of the airways.