Cough Hypersensitivity Induced by Eosinophil Granule‐Derived Major Basic Protein in Awake Mice

Abstract

Non‐asthmatic eosinophilic bronchitis is one of the major causes of chronic cough. Major basic protein (MBP), an eosinophil granule‐derived cationic protein, is known to induce airway mucosal inflammation and hypersensitivity of airway sensory nerves. However, little is known about the effects of MBP on cough sensitivity. This study was carried out to determine the effect of MBP on modulating cough responses to inhalation of sulfur dioxide (SO2) and ammonia (NH3), air pollutants and chemical irritants, in a murine model. Awake mice were each placed in a recording chamber that was ventilated with a constant flow (300 ml/min) of air or irritant gas mixture. Coughs were detected by analyzing the pressure changes inside the chamber and in the intrapleural space (via telemetry), in conjunction with the audio and video signals recorded simultaneously. Cough responses to SO2 and NH3 inhalation (300 and 600 ppm, 0.1% and 0.2% balanced in air) were determined for 3 days before and ~10 days after 0.02 mg of MBP instillation into the trachea of the mouse. Our preliminary data obtained in 8 mice (the group of SO2 inhalation) and 6 mice the group of NH3 inhalation) showed: 1) inhalation of SO2 elicited cough responses in a dose‐dependent manner; 2) after the administration of MBP, cough responses to both concentrations of SO2 were significantly elevated; 3) the cough hyperresponsiveness to SO2 reached the peak ~2 days after the MBP treatment, and returned to baseline after ~7 days; 4) inhalation of NH3 also elicited cough responses in a dose‐dependent manner, which was augmented after the MBP treatment in a pattern similar to that of SO2. In conclusion, these findings suggest a possible role of MBP in the chronic cough associated with eosinophilic bronchitis.Support or Funding InformationNIH grants UL1TR001998 and AI123832This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.