Role of mast cells, eosinophils and IL-5 in the development of airway hyperresponsiveness in sensitized mice.
OBJECTIVE
In order to study the role of mast cells and IL-5 in allergen-induced airway hyperreactivity in mice, airway responsiveness in WBB6F1-W/Wv mice (mast cell deficient) and the effects of anti-IL-5 monoclonal antibody (NC-17) and three anti-allergic drugs (N-556, ketotifen and amlexanox) on airway hyperreactivity in Balb/c mice were studied.


METHODS
Mice were immunized with an antigen (ovalbumin; OA) at intervals of 12 days. OA was inhaled 10 days after the secondary immunization. Twenty-four hours after the last inhalation, airway reactivity to acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was obtained.


RESULTS
Three inhalations of OA caused an increase in leucocytes (including eosinophils), accompanied by increases in IL-5 in BALF, and airway hyperreactivity to acetylcholine in Balb/c and WBB6F1- +/+ mice. In WBB6F1-W/Wv mice, antigen inhalation resulted in increases in leucocytes and IL-5 in BALF but did not result in airway hyperreactivity. NC-17 at doses between 10 and 20 micrograms (intratracheal injection) inhibited the antigen-induced eosinophilia but did not affect airway hyperreactivity in Balb/c mice. Three 'anti-allergic' drugs clearly inhibited antigen-induced increases in IL-5 levels and the number of eosinophils in BALF, but did not affect airway hyperreactivity in Balb/c mice.


CONCLUSIONS
These data suggest that mast cells play an important role in the onset of airway hyperreactivity but do not play a role in the production of IL-5 and eosinophilia. Furthermore, indicate that the inhibition of IL-5 is not always associated with a reduction in antigen-induced airway hyperreactivity in mice.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Yamaguchi
S
S
Maeda
Y
Y
Tanaka
H
H
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D002867:Chromones / Q000494:pharmacology; D004804:Eosinophils / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology*; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011355:Prodrugs / Q000494:pharmacology
D000631:Aminopyridines; D018926:Anti-Allergic Agents; D000911:Antibodies, Monoclonal; D002867:Chromones; D015848:Interleukin-5; D011355:Prodrugs; C069179:N 556; C045742:amlexanox; D007665:Ketotifen