Nerve growth factor-induced substance P in capsaicin-insensitive vagal neurons innervating the lower mouse airway.
BACKGROUND
Nerve growth factor (NGF) is elevated in allergic diseases such as bronchial asthma and can lead to an induction of substance P (SP) and related neuropeptides in guinea-pigs large-diameter, neurofilament-positive airway neurons.


OBJECTIVE
In the present study, the effect of NGF on tyrosine kinase receptor trkA and the capsaicin receptor TRPV1 expression in airway-specific vagal sensory neurons located in the jugular-nodose ganglia complex (JNC) of mice was investigated.


METHODS
Using retrograde neuronal tracing in combination with double-labelling immunohistochemistry, SP, trkA- and TRPV1-receptor expression was examined in airway-specific sensory neurons of BALB/c mice before and after NGF treatment.


RESULTS
NGF injected into the lower airway was able to induce SP (13.0+/-2.03% vs. 5.9+/-0.33%) and trkA expression (78+/-2.66% vs. 60+/-2.11%) in larger diameter (>25 microm), capsaicin-insensitive and trkA-positive vagal sensory neurons that were retrograde-labelled with Fast Blue dye from the main stem bronchi.


CONCLUSIONS
Based on the extent of SP and trkA co-expression in airway-specific neurons by NGF treatment, the present study suggests that, following a peripheral activation of trkA receptor on SP afferent by NGF which is elevated in allergic inflammation, there may be trkA-mediated SP induction to mediate neurogenic airway inflammation.
Dinh
Q T
QT
Department of Medicine, Charité-Humboldt University, Berlin, Germany. q-thai.dinh@charite.de
Groneberg
D A
DA
Peiser
C
C
Springer
J
J
Joachim
R A
RA
Arck
P C
PC
Klapp
B F
BF
Fischer
A
A
D000818:Animals; D002211:Capsaicin / Q000276:immunology*; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D007473:Ion Channels; D051379:Mice; D008807:Mice, Inbred BALB C; D020932:Nerve Growth Factor / Q000276:immunology*; D009475:Neurons, Afferent / Q000276:immunology*; D009620:Nodose Ganglion / Q000276:immunology*; D020917:Receptor, trkA / Q000032:analysis / Q000276:immunology; D012137:Respiratory System / Q000276:immunology* / Q000294:innervation; D013373:Substance P / Q000276:immunology*; D050916:TRPV Cation Channels
D007473:Ion Channels; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D013373:Substance P; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D002211:Capsaicin