Airway eosinophil accumulation on sensory neuropeptide release in a guinea pig model of distilled-water-induced bronchoconstriction.
BACKGROUND
Increased numbers of eosinophils in the airways is characteristic of asthma. However, it remains unclear whether airway eosinophils enhance or reduce the release of neuropeptides in the airways in vivo. This study was conducted to elucidate the influence of airway eosinophil accumulation on the ultrasonically nebulized distilled water (UNDW)-induced bronchoconstriction in our newly developed animal model, which is mediated by sensory neuropeptides.


METHODS
Guinea pigs were transnasally treated with 100 mg/kg of platelet activating factor (PAF), or vehicle, twice a week for 3 weeks. We then conducted three experiments. In the first, UNDW was inhaled 20 min after aerosolized antigen challenge, and bronchoalveolar lavage (BAL) was performed in PAF-treated and passively sensitized animals. In the second, PAF-treated animals were exposed for 20 s to ascending doses of methacholine at intervals of 5 min In the third, passively sensitized animals were administered selective NK1 antagonist, SR 140333, selective NK2 antagonist, SR 48968, or vehicle, intravenously 5 min before UNDW-induced bronchoconstriction.


RESULTS
The proportion of eosinophils in BAL fluid was significantly increased in guinea pigs treated with PAF, compared with the vehicle. The PAF treatment did not affect antigen-induced immediate asthmatic response, UNDW-induced bronchoconstriction, or bronchial responsiveness to inhaled methacholine. SR 140333, but not SR 48968, inhibited the UNDW-induced bronchoconstriction.


CONCLUSIONS
We conclude that eosinophils accumulated in the airways, caused by repeated intranasal administration of PAF, does not affect the release of substance P induced by UNDW inhalation, or the action of released substance P in vivo.
Ishiura
Yoshihisa
Y
Kanazawa Graduate University School of Medicine, Kanazawa, Japan. ishiura-@p2322.nsk.ne.jp
Fujimura
Masaki
M
Myou
Shigeharu
S
Amemiya
Tokunao
T
Nobata
Kouichi
K
Kurashima
Kazuyoshi
K
Nonomura
Akitaka
A
D000336:Aerosols; D000818:Animals; D001980:Bronchi / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology* / Q000382:microbiology; D016084:Bronchoconstriction / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D006168:Guinea Pigs; D007116:Immunization, Passive; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism*; D014867:Water / Q000008:administration & dosage
D000336:Aerosols; D010880:Piperidines; D010972:Platelet Activating Factor; D011812:Quinuclidines; D014867:Water; D016210:Methacholine Chloride; C085215:SR 140333; D013373:Substance P