Selective nasal allergen provocation induces substance P-mediated bronchial hyperresponsiveness.
Although the concept of "global airway allergy" has become widely accepted during recent years, nasobronchial interaction and its mechanisms remain incompletely understood. The experimental study of the effect of nasal allergen deposition on lower airway pathology is hampered by the difficulty of avoiding lower airway penetration of the allergens. In ovalbumin-sensitized mice with experimental airway allergy, nasal allergen provocations were performed after complete anatomical separation of upper and lower airways by means of a tracheotomy. A canula was inserted in the trachea, and the trachea was ligated, thus inhibiting any passage of allergens from upper to lower airways. Mice showed bronchial hyperresponsiveness to methacholine as early as 4 hours after nasal allergen provocation in the absence of recruitment of inflammatory cells. An increased substance P (SP) concentration in the bronchial lumen was found, as well as an increased number of SP-positive pulmonary nerves. Treatment with a neurokinin (NK) 1 receptor antagonist abolished the allergen-induced bronchial hyperresponsiveness. Moreover, endobronchial administration of SP caused NK1 receptor-dependent bronchial hyperresponsiveness in mice with airway allergy. Nasal allergen provocation rapidly induces bronchial hyperresponsiveness via pulmonary up-regulation of SP and activation of NK1 receptors.
University Hospital Leuven, Division of Otorhinolaryngology, Kapucijnevoer 33, 3000 Leuven, Belgium.
Greet
G
Hens
Ulrike
U
Raap
Jeroen
J
Vanoirbeek
Isabelle
I
Meyts
Ina
I
Callebaut
Bert
B
Verbinnen
Bart M
BM
Vanaudenaerde
Pascal
P
Cadot
Benoit
B
Nemery
Dominique M A
DM
Bullens
Jan L
JL
Ceuppens
Peter W
PW
Hellings
D000280:Administration, Inhalation; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000276:immunology* / Q000473:pathology; D007114:Immunization; D007958:Leukocyte Count; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009299:Nasal Provocation Tests; D064729:Neurokinin-1 Receptor Antagonists; D010047:Ovalbumin / Q000276:immunology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000485:Allergens; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D016210:Methacholine Chloride; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; D013373:Substance P; D014364:Tryptophan; D010047:Ovalbumin