Airway hypersensitivity induced by eosinophil granule-derived cationic proteins

Area of Science:

• Neuroscience
• Pulmonology
• Cell Biology

Background:

• Airway hypersensitivity is a key feature of inflammatory airway diseases.
• Eosinophil granule-derived cationic proteins contribute to airway mucosal damage and bronchial hyperresponsiveness.

Purpose of the Study:

• To investigate the effects of cationic proteins on vagal bronchopulmonary C-fiber afferents.
• To elucidate the mechanisms underlying cationic protein-induced airway C-fiber sensitization.

Main Methods:

• Administration of cationic proteins (e.g., major basic protein, poly-l-lysine) via intra-tracheal instillation in rats and mice.
• Electrophysiological recordings from isolated rat bronchopulmonary neurons.
• Assessment of cough responses to irritant gases in awake mice.

Main Results:

• Cationic proteins induced intense C-fiber discharge and enhanced their sensitivity to chemical and mechanical stimuli.
• These effects were dependent on the cationic charge and were reversible.
• Cationic proteins inhibited voltage-gated K+ currents in capsaicin-sensitive neurons.
• In vivo, major basic protein increased cough responses in mice.

Conclusions:

• Enhanced sensitivity of bronchopulmonary C-fibers by eosinophil cationic proteins is a potential mechanism for bronchial hyperresponsiveness.
• These findings suggest a role for cationic proteins in the pathogenesis of chronic cough and airway inflammation associated with eosinophilic diseases.