Die Rolle der CDR-H3-Region in einem murinen Modell der chronisch allergischen Atemwegsentzündung
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Philipps-Universität Marburg
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Abstract
Immunoglobuline E (IgE) is a central effector molecule in allergic immune responses. Bound to mast cells, IgE generates the immunological interface between allergen and immune system. It has been demonstrated that modifications of the classical antigen binding-site (CDR-H3) have significant impact on the asthma phenotype in a murine model of acute allergic airway inflammation. However, the airway hyperreactivity remained unaffected.
Therefore, the objective of this study was to determine the impact of qualitative changes in the CDR-H3 in a chronic model of allergic asthma. Transgenic mice with preferentially charged CDR-H3 (ΔDid-mice) were sensitized to ovalbumin. Subsequently, chronic airway inflammation was induced by 22 consecutive challenges with aerosolic ovalbumin over a period of 104 days. ΔDid-mice were compared to wildtype mice (wt) and to non-sensitized controls.
ΔDid- and wt mice showed a significant rise in total serum IgE during allergic sensitization. However, this rise was alleviated in ΔDid-mice. This attenuation was reflected in ovalbumin-specific IgE levels. In ΔDid-mice, the rise in allergen-specific IgE levels was reduced. Moreover, ΔDid-mice showed a diminished count of eosinophils in bronchoalveolar lavage fluids compared to wt. To assess lung function, head-out body plethysmography was used. Sensitized wt mice developed dose-dependent airway hyperresponsiveness to methacholine. In contrast, in ΔDid-mice the airway hyperresponsiveness was completely abolished.
In conclusion, modifications of the CDR-H3-region significantly attenuate the asthma phenotype in a murine model of chronic allergic airway inflammation. The airway hyperreactivity even is prevented by a modification of the CDR-H3- region.
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Dates
Created: 2011Issued: 2011-10-21Updated: 2011-10-24
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
murine modellallergic asthmaairway hyperreagibilityairway remodellingAtemwegsreagibilitätCDR-H3-Region
DFG-subjects
BALB/c MausImmunglobulin EAllergisches Asthma
DDC-Numbers
610
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Preisser, Kathrin: Die Rolle der CDR-H3-Region in einem murinen Modell der chronisch allergischen Atemwegsentzündung. : Philipps-Universität Marburg 2011-10-21. DOI: https://doi.org/10.17192/z2011.0571.
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This item has been published with the following license: In Copyright