Allergen-induced substance P synthesis in large-diameter sensory neurons innervating the lungs.
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.


CONCLUSIONS
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.
Chuaychoo
Benjamas
B
Johns Hopkins University School of Medicine and Bloomberg School of Public Health, USA.
Hunter
Dawn D
DD
Myers
Allen C
AC
Kollarik
Marian
M
Undem
Bradley J
BJ
D000485:Allergens / Q000276:immunology*; D000818:Animals; D006967:Hypersensitivity / Q000378:metabolism*; D008168:Lung / Q000294:innervation*; D008297:Male; D051379:Mice; D009620:Nodose Ganglion / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D013373:Substance P / Q000096:biosynthesis*; D014628:Vagotomy
D000485:Allergens; D013373:Substance P; D010047:Ovalbumin