Article Text

THE AIRWAY HYPERREACTIVITY IN A MURINE MODEL OF CHRONIC ASTHMA IS PREVENTED BY MODIFICATIONS OF THE CLASSICAL ANTIGENBINDING SITE CDRH3
  1. S Kerzel1,
  2. K Preisser1,
  3. T Rogosch1,
  4. H W Schroeder2,
  5. R F Maier1,
  6. M Zemlin1
  1. 1Department of Pediatrics, PhilippsUniversity Marburg, Marburg, Germany
  2. 2Developmental and Clinical Immunology University of Alabama at Birmingham, Birmingham, AL, USA

Abstract

Immunoglobulin 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. We previously demonstrated that modifications of the classical antigen bindingsite CDRH3 have significant impact on the asthma phenotype in a murine model of acute allergic airway inflammation. However, the airway hyperreactivity remained unaffected.

Therefore, we now examined the impact of qualitative changes in the CDRH3 in a chronic model of allergic asthma. Transgenic mice with preferentially charged CDRH3 Didmice were sensitized to ovalbumin. Subsequently, chronic airway inflammation was induced by 22 consecutive challenges with aerosolic ovalbumin over a period of 104days. Didmice were compared to wildtype mice wt and to nonsensitized controls.

Did n34 and wt mice n36 showed a significant rise in total serum IgE during allergic sensitization. However, this rise was alleviated in Didmice 377 compared to wt p0.001. This attenuation was reflected in ovalbuminspecific IgE levels. In Didmice, the rise in allergenspecific IgE levels was reduced 5414 compared to wt p0.05. Moreover, Didmice showed a diminished count of eosinophils in bronchoalveolar lavage fluids 214 compared to wt. To assess lung function, we used headout body plethysmography. Sensitized wt mice developed dosedependent airway hyperresponsiveness to methacholine. In contrast, in Didmice the airway hyperresponsiveness was completely abolished p0.05.

In conclusion, the airway hyperreactivity in a murine model of chronic asthma is prevented by modifications of the classical antigenbinding site CDRH3.

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