Mechanisms of bronchopulmonary C-fiber hypersensitivity induced by cationic proteins

Lu Yuan Lee, Qihai Gu

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations


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.

Original languageEnglish
Pages (from-to)15-22
Number of pages8
JournalPulmonary Pharmacology and Therapeutics
Issue number1
StatePublished - Feb 2003

Bibliographical note

Funding 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
  • Asthma
  • Eosinophil
  • Mucosal inflammation
  • Pulmonary C fibers

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)


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