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.