title: Absence of late airway response despite increased airway responsiveness and eosinophilia in a murine model of asthma.
abstract: In asthmatics an immediate asthmatic response occurs after antigen provocation. Furthermore, asthmatic patients display airway hyperresponsiveness, accompanied by airway eosinophilia. In some patients late asthmatic responses can be detected. Many controversies still exist about the relations between the different airway responses and inflammatory cell infiltration, we therefore used a murine model to investigate associations between these phenomena. In this study we show the presence of antigen-induced early bronchoconstrictive responses, accompanied by increased serum mucosal mast cell protease-1 (MMCP-1) levels. However, we were unable to demonstrate late bronchoconstrictive responses either at the time when eosinophils start to infiltrate the lungs or when both airway hyperresponsiveness and eosinophilia are established. With sequential exposures to antigen, an association exists between development of airway hyperresponsiveness and eosinophilia. In contrast, resolution of this hyperreactivity appears to be dissociated from eosinophilia after stopping the antigen challenges. Based on these data, we conclude that mast cell degranulation is a plausible cause of early bronchoconstrictive responses. Furthermore, late bronchoconstrictive responses are not related to the infiltration of eosinophils or development of airway hyperresponsiveness in this murine model. Finally, we conclude that airway hyperresponsiveness and eosinophilia are only associated with each other during the induction phase and not after the final antigen challenge.
authors.affiliation: Department of Pharmacology and Pathophysiology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: de Bie
authors.forename: M
authors.initials: M
authors.lastname: Kneepkens
authors.forename: A D
authors.initials: AD
authors.lastname: Kraneveld
authors.forename: E H
authors.initials: EH
authors.lastname: Jonker
authors.forename: P A
authors.initials: PA
authors.lastname: Henricks
authors.forename: F P
authors.initials: FP
authors.lastname: Nijkamp
authors.forename: A J
authors.initials: AJ
authors.lastname: van Oosterhout
mesh_terms: D000818:Animals; D001249:Asthma / Q000097:blood* / Q000139:chemically induced / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000209:etiology* / Q000473:pathology; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D010993:Plethysmography, Whole Body; D013997:Time Factors
chemical_list: D010047:Ovalbumin