Chemosensitivity of Tachykinin-Containing Lung Afferents

  • Lee, Lu (PI)
  • Gu, Qihai (CoI)
  • Vanaman, Thomas (CoI)

Grants and Contracts Details


Vagal bronchopulmonary C-fiber sensory nerves play an important role in regulating airway functions. Hypersensitivity of these afferents is believed to be involved in the manifestation of airway hyperresponsiveness associated with mucosal injury, a prominent feature of asthma. During airway inflammatory reaction, a number of low molecular weight, highly cationic proteins are secreted by inflammatory cells such as eosinophils that infiltrate into the airways. It is well documented that the release of these proteins can induce mucosal injury and airway hyperresponsiveness. Our recent studies have established the first direct evidence demonstrating an intense and sustained effect of both human eosinophil granule-derived and synthetic cationic proteins on vagal bronchopulmonary C-fiber endings. However, the mechanism underlying both the initial stimulatory and the sustained sensitizing effects of cationic proteins on these sensory nerves is poorly understood. Our central hypothesis is that the cationic charge carried by these proteins acts on the airway mucosa, triggering the release of certain inflammatory mediators that in turn exert potent effects on the C-fiber terminals. The mast cells located in the airway mucosa probably play an important role in the interaction between cationic proteins and sensory endings. Sensitization of these afferents can then lead to airway hyperresponsiveness via both cholinergic reflex pathways and tachykininergic mechanisms. Single-fiber and whole-cell patch-clamp recording techniques will be employed to measure the activity of bronchopulmonary C fibers in anesthetized rats and in isolated neurons, respectively. The results obtained from this study should provide critical information for gaining new insights into the mechanisms underlying the airway hyperresponsiveness induced by cationic proteins.
Effective start/end date4/1/986/30/11


  • National Heart Lung and Blood Institute: $972,764.00


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