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Am. J. Respir. Crit. Care Med., Volume 161, Number 6, June 2000, 1985-1990

Nerve Growth Factor-Induced Phenotypic Switch in Guinea Pig Airway Sensory Neurons

DAWN D. HUNTER, ALLEN C. MYERS, and BRADLEY J. UNDEM

The Johns Hopkins Medical Institution, Department of Medicine, Division of Clinical Immunology, The Asthma and Allergy Center, Baltimore, Maryland

Immunohistochemistry was combined with retrograde tracing techniques to characterize the effect of nerve growth factor (NGF) on substance P (SP) producing vagal neurons innervating the guinea pig trachea. Fast blue dye instilled into the trachea retrogradely labeled nerve cell bodies located in the nodose and jugular ganglia. In untreated guinea pigs > 99% of the SP-containing neurons labeled with fast blue were located in the jugular ganglia. The SP-positive neurons were small in diameter (23 ± 1 µm) and were negative for neurofilament immunoreactivity. The fast-blue-positive neurons in the nodose ganglia, by contrast, were large in diameter (40 ± 3 µm) and were negative for SP immunoreactivity and positive for neurofilament immunoreactivity. After NGF-beta injections into the tracheal wall, approximately 10% of the large-diameter nodose neurofilament-positive neurons projecting fibers to the trachea became SP-positive (p < 0.05). We previously demonstrated that nodose nerve endings supplying the trachea are exquisitely mechanically sensitive, but capsaicin- and bradykinin-insensitive. These results suggest that NGF not only increases SP expression in airway neurons, but changes the neuronal phenotype such that large, capsaicin-insensitive nodose neurons with fast-conducting "Adelta " fibers provide a component of the tachykinergic innervation.




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