Airway hypersensitivity induced by eosinophil granule-derived cationic proteins

Publication date: Available online 13 May 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Lu-Yuan Lee, Qihai Gu, An-Hsuan Lin, Mehdi Khosravi, Gerald GleichAbstractVagal bronchopulmonary C-fiber sensory nerves play an important role in the manifestation of airway hypersensitivity, a common and prominent pathophysiological feature of airway inflammatory diseases. Eosinophil granule-derived cationic proteins are known to be involved in the mucosal damage and development of bronchial hyperresponsiveness during allergic airway inflammation. In view of these background information, we have carried out a series of studies to investigate the effect of cationic proteins on these C-fiber afferents and the mechanism(s) possibly involved; a summary of these studies is presented in this mini-review. Intra-tracheal instillation of either eosinophil granule-derived (e.g., major basic protein, MBP) or synthetic cationic proteins (e.g., poly-l-lysine) induced a sporadic, but intense and lingering discharge of pulmonary C-fibers, and greatly enhanced the chemical and mechanical sensitivities of these afferents in anesthetized rats. The stimulatory and sensitizing effects of these proteins were completely nullified when their cationic charges were neutralized or removed. Furthermore, in isolated rat bronchopulmonary capsaicin-sensitive neurons, eosinophil granule cationic proteins induced a direct and long-lasting (>60 min) but reversible sensitizing effect on their responses to ...
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research