Pneumologie 2015; 69 - A30
DOI: 10.1055/s-0035-1556622

Airway surface dehydration is a novel risk factor for allergic airway inflammation

B Fritzsching 1, L Dai 1, C van Bodegom 1, J Schatterny 1, S Hirtz 1, Z Zhou-Suckow 1, M Hagner 1, S Christochowitz 1, MA Mall 1
  • 1Department of Translational Pumonology, Translational Lung Research Center (TLRC), University of Heidelberg

Introduction: We have previously demonstrated that mice with airway specific overexpression of the amiloride-sensitive epithelial Na+ channel (βENaC-Tg) and mice lacking the epithelial Cl- channel SLC26A9 suffer from airway surface dehydration and airway mucus obstruction, which might be implicated in the pathogenesis of allergic airway disease (Anagnostopoulou et al., JCI 2012 and Mall et al., AmJRespirCritCare Med 2008). Here, we hypothesized that airway surface dehydration and reduced mucociliary clearance may increase the susceptibility for allergic airway inflammation.

Methods: Aspergillus fumigatus extract (Af) was applied by intratracheal instillations into juvenile βENaC-Tg mice or WT mice (C57BL/6) and BAL cell counts, IL-13 levels and airway hyperresponsiveness (AHR, by Flexivent lung function) were determined. Genetic deletion of the IL-4/IL13 receptor signal transducer STAT6 was introduced to βENaC-Tg mice to analyze the contribution of type 2 inflammation to the Af immune response. Furthermore, preventive treatment of βENaC-Tg mice and WT mice with amiloride was performed and BAL and IL-13 levels were determined.

Results: Airway eosinophils and pulmonary IL-13 expression were significantly increased in Af-challenged compared to vehicle-treated βENaC-Tg mice. Airway hyperresponsiveness was elevated in βENaC-Tg mice and increased further in response to Af treatment. Genetic deletion of STAT6 abrogated Af-induced airway eosinophilia and IL-13 expression in βENaC-Tg mice. Preventive treatment with amiloride significantly reduced allergic inflammataion in both βENaC-Tg and WT mice.

Conclusion: Collectively, our results indicate that airway surface dehydration is a risk factor for key pathologies in allergic airway disease. Amelioration of airway surface dehydration (i.e. by amiloride) might constitute a novel target for prevention and treatment of allergic airway disease.

Acknowledgements: DFG (DFG MA 2081/3 – 2)

*Presenting author