title: Mechanisms of bronchopulmonary C-fiber hypersensitivity induced by cationic proteins.
abstract: 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.
authors.affiliation: Department of Physiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536-0298, USA. lylee@uky.edu
authors.forename: Lu-Yuan
authors.initials: LY
authors.lastname: Lee
authors.forename: Qihai
authors.initials: Q
authors.lastname: Gu
mesh_terms: D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D002412:Cations; D004594:Electrophysiology; D004804:Eosinophils / Q000276:immunology / Q000502:physiology; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology; D008168:Lung / Q000276:immunology / Q000294:innervation* / Q000502:physiology*; D036421:Nerve Fibers, Unmyelinated / Q000276:immunology / Q000502:physiology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D014630:Vagus Nerve
chemical_list: D002412:Cations; D011506:Proteins