Bronchoconstriction and airway hyperresponsiveness after ovalbumin inhalation in sensitized mice.
To investigate the mechanisms underlying airway hyperresponsiveness a murine model was developed with several important characteristics of human allergic asthma. Mice were intraperitoneally sensitized with ovalbumin and after 4 weeks challenge via an ovalbumin aerosol. After aerosol, lung function was evaluated with a non-invasive forced oscillation technique. The amount of mucosal exudation into the airway lumen and the presence of mast cell degranulation was determined. Tracheal responsiveness was measured at several time points after challenge. At these time points also bronchoalveolar lavage and histology were performed. Sensitization induced high antigen-specific IgE levels in serum. Inhalation of ovalbumin in sensitized mice induced an immediate but no late bronchoconstrictive response. During this immediate phase, respiratory resistance was increased (54%). Within the first hour after ovalbumin inhalation increased mucosal exudation and mast cell degranulation were observed. At 12 and 24 h after ovalbumin challenge, mice showed tracheal hyperresponsiveness (29% and 34%, respectively). However, no apparent inflammation was found in the lungs or bronchoalveolar lavage. From these results it can be concluded that hyperresponsiveness can develop via mechanisms independent of an inflammatory infiltrate. Since mast cell degranulation occurred after ovalbumin exposure, we hypothesize that mast cells are involved in the induction of airway hyperresponsiveness in this model.
Hessel
E M
EM
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Netherlands.
Van Oosterhout
A J
AJ
Hofstra
C L
CL
De Bie
J J
JJ
Garssen
J
J
Van Loveren
H
H
Verheyen
A K
AK
Savelkoul
H F
HF
Nijkamp
F P
FP
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D018893:Bronchoalveolar Lavage; D016084:Bronchoconstriction; D017449:Dermatitis, Allergic Contact / Q000209:etiology; D005122:Exudates and Transudates; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D066298:In Vitro Techniques; D008168:Lung / Q000473:pathology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced*; D014132:Trachea / Q000473:pathology
D007074:Immunoglobulin G; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin