Cationic proteins secreted by inflammatory cells infiltrating into the airways are known to cause mucosal injury and bronchial hyperresponsiveness. Although an involvement of bronchopulmonary C-fiber afferents in the cationic protein-induced airway hyperresponsiveness has been suggested, direct electrophysiological evidence has not been established. Accordingly, a series of studies was recently carried out using the single-fiber recording technique to determine the responses of pulmonary C fibers to cationic proteins and to investigate the mechanisms possibly underlying these effects. Intratracheal instillation of either human eosinophil granule-derived cationic proteins or synthetic cationic proteins induced a sporadic but intense stimulatory effect on pulmonary C fibers and greatly enhanced the sensitivities of these afferents to both lung inflation and chemical stimuli in anesthetized rats. These responses developed slowly (latency: 20-40s), reached peak in 2-10 min, then gradually declined. The effects of synthetic cationic proteins sustained for >60 min. When administered by intravenous injection or instilled into a different region of the lung, the same cationic proteins had no effect on the C-fiber endings, even at a higher dose. Furthermore, the stimulatory and sensitizing effects of these proteins were completely nullified when their cationic charges were neutralized with negatively charged heparin before delivery. However, heparin administered 5-10 min after the delivery of cationic proteins was ineffective in reversing the effects. In conclusion, intratracheal instillation of cationic proteins consistently induces intense stimulation and sensitization of pulmonary C fibers, and an interaction between the cationic charges carried by these proteins and the airway mucosa is probably responsible.
|Number of pages||8|
|Journal||Pulmonary Pharmacology and Therapeutics|
|State||Published - Feb 2003|
Bibliographical noteFunding Information:
The authors are grateful to Dr You-Shuei Lin and Robert Morton for technical assistance, and to Dr Gerald Gleich and his coworkers at the Mayo Clinic (Rochester, Minnesota) for providing the human eosinophil granule-derived cationic proteins. This study was supported by grants HL58686 and HL67379 from the National Institutes of Health.
- Airway hyperresponsiveness
- Mucosal inflammation
- Pulmonary C fibers
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Biochemistry, medical
- Pharmacology (medical)