Abstract
Background: Tachykinins such as substance P are localized in unmyelinated slow-conducting C fibers that can be activated by noxious stimuli and tissue inflammation. Substance P is seldom expressed in fast-conducting large-diameter (A-fiber) vagal sensory neurons. We have previously found that allergic inflammation causes a phenotypic change in tachykinergic innervation of the trachea such that the production of substance P is induced in large-diameter sensory neurons projecting mechanosensitive A fibers to the trachea. Objective: To evaluate whether allergic inflammation also induces substance P synthesis in large-diameter sensory stretch-receptor neurons innervating guinea pig lungs, and to investigate potential mechanisms by which this may occur. Methods: Sensitized guinea pigs were exposed to allergen (ovalbumin) aerosol. One day later, immunohistochemical analysis was performed on vagal sensory neurons that had been retrogradely labeled from the lungs. Results: Ovalbumin inhalation caused a significant increase in substance P expression in large-diameter neurofilament-positive nodose ganglion neurons that innervate the lungs (P < .05). This effect was decreased by ipsilateral vagotomy. Exposing isolated nodose ganglia to the sensitizing antigen, ovalbumin, also significantly increased substance P expression compared with control. Conclusion: Allergic inflammation induces substance P synthesis in large-diameter (A-fiber) nodose ganglion neurons innervating guinea pig lungs. This could contribute to the hyperreflexia seen in allergic airway disease. The full expression of this phenotypic switch in vagus nodose ganglion neurons requires intact vagus nerve, but if allergen reached the systemic circulation in sufficient quantities, it could also affect substance P synthesis by local activation of vagal ganglionic mast cells.
Original language | English (US) |
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Pages (from-to) | 325-331 |
Number of pages | 7 |
Journal | Journal of Allergy and Clinical Immunology |
Volume | 116 |
Issue number | 2 |
DOIs | |
State | Published - Aug 2005 |
Keywords
- Allergic inflammation
- Neurogenic inflammation
- Nodose ganglion
- Phenotypic switch
- Sensory nerve
- Substance P
- Vagus nerve
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology