Modulation of neurotrophin and neurotrophin receptor expression in nasal mucosa after nasal allergen provocation in allergic rhinitis.
BACKGROUND
Patients with allergic rhinitis (AR) feature both allergic airway inflammation and a hyperresponsiveness to nonspecific stimuli which is partly neuronally controlled. Still, it is unclear whether or not neurotrophins are involved in airway pathophysiology of AR and in nasobronchial interaction.


METHODS
Nine AR patients with mono-allergy to grass pollen and nine healthy controls underwent nasal allergen provocation (NP). Serum samples, nasal and bronchial biopsies were taken before (T(0)) and 24 h after (T(24)) NP. Pan-neurotrophin receptor p75(NTR), tyrosine kinase A (trkA), trkB, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) were assessed with immunohistochemistry, and NGF and BDNF levels with ELISA.


RESULTS
At T(24), BDNF and NGF were upregulated in nasal mucosa (P < 0.05) and increased in the peripheral blood of AR compared with T(0). The increase in nasal BDNF expression correlated positively with the maximum increase in total nasal symptom score in AR (P = 0.02). p75(NTR) was expressed on peripheral nerves and epithelial layer, trkA on endothelial cells, and trkB on mast cells. trkB + mast cells significantly decreased after NP in AR (P < 0.01). NP did not modulate p75(NTR) and trkA expression in nasal mucosa and had no effect on the expression of neurotrophins and receptors in bronchial mucosa.


CONCLUSIONS
This study shows that neurotrophins and their receptors are expressed in human airways. Allergic rhinitis was characterized by a modulation of BDNF, NGF, and trkB in nasal mucosa after NP and a correlation of nasal BDNF with the maximal increase of total nasal symptom score. Therefore, our data suggest that neurotrophins participate in upper-airway pathophysiology in AR, whereas their role in nasobronchial interaction remains unclear.
Raap
U
U
Department of Dermatology and Allergology, Hannover Medical University, Hannover, Germany.
Fokkens
W
W
Bruder
M
M
Hoogsteden
H
H
Kapp
A
A
Braunstahl
G-J
GJ
D000328:Adult; D000485:Allergens; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000276:immunology*; D001980:Bronchi / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000276:immunology; D009296:Nasal Cavity / Q000276:immunology; D009299:Nasal Provocation Tests; D020932:Nerve Growth Factor / Q000097:blood / Q000276:immunology*; D006109:Poaceae / Q000276:immunology; D011058:Pollen / Q000276:immunology; D020800:Receptor, Nerve Growth Factor / Q000276:immunology*; D020917:Receptor, trkA / Q000276:immunology*; D020813:Receptor, trkB / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000276:immunology*
D000485:Allergens; D019208:Brain-Derived Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB