Murine model for non-IgE-mediated asthma.
There is increasing evidence that inflammatory mechanisms other than atopy or eosinophilic inflammation may be involved in the pathogenesis of asthma. The mechanisms associated with non-atopic (non-IgE) or neutrophil-mediated asthma are poorly investigated. Non-atopic airway inflammation and hyperresponsiveness was induced in mice by skin sensitization with dinitrofluorobenzene (DNFB) followed by intra-airway challenge with dinitrobenzene sulfonic acid (DNS). Acute bronchoconstriction and mast cell activation were observed shortly after challenge. Increased levels of the major mast cell mediator, TNF-alpha, were found in the bronchoalveolar lavage fluid of DNFB-sensitized. Mast cells play a key role in the early release of TNF-alpha since mast-cell-deficient WBB6F1-W/Wv mice did not show an increase in TNF-alpha release after DNFB-sensitization and DNS challenge compared to their ++ littermates. Features of the late-phase pulmonary reaction included mononuclear and neutrophilic cell infiltration, pulmonary edema, in vitro tracheal hyperreactivity and in vivo airway hyperresponsiveness. These characteristics bear marked similarity with those observed in non-atopic asthmatic patients. Therefore, this model can be used to further study the mechanisms potentially responsible for the development of non-IgE-mediated asthma.
van der Kleij
Hanneke P M
HP
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. j.p.m.vanderkleij@pharm.uu.nl
Kraneveld
Aletta D
AD
van Houwelingen
Anneke H
AH
Kool
Mirjam
M
Weitenberg
Andrys C D
AC
Redegeld
Frank A M
FA
Nijkamp
Frans P
FP
D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000276:immunology* / Q000503:physiopathology; D002217:Carbachol / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000276:immunology / Q000503:physiopathology; D004139:Dinitrofluorobenzene / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007073:Immunoglobulin E / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D007073:Immunoglobulin E; D002217:Carbachol; D004139:Dinitrofluorobenzene