Pneumologie 2015; 69 - A18
DOI: 10.1055/s-0035-1556610

Acute cigarette smoke accelerate chronic bronchitis development in ENaC overexpressing newborn-mice

J Jia 1, TM Conlon 1, C Ballester López 1, O Eickelberg 1, 2, MA Mall 3, A Önder Yildirim 1
  • 1Comprehensive Pneumology Center (CPC), Institute of Lung Biology and Disease, Helmholtz Zentrum München, German Center for Lung Research (DZL)
  • 2University Hospital of the Ludwig Maximilians University (LMU), Munich, Germany
  • 3Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, University of Heidelberg, Germany

Chronic bronchitis (CB) is characterized by mucus accumulation, airway neutrophilia, and chronic airway obstruction. Excess mucus production, together with less efficient cough and loss of normal ciliary function, leads to recurrent respiratory obstruction. Overexpression of Na+ ion channels (bENaC) in the airway epithelial membrane of mice leads to airway surface liquid depletion and mucocilia clearance dysfunction, resulting in airway mucus accumulation and subsequent COPD-like disease (Mall et al. AJRCCM 2008). Cigarette smoke (CS) exposure is the major factor that causes non-infectious chronic bronchitis. Therefore, we hypothesize that cigarette smoke exposure induces mucus production and inflammation which enhances the progression of obstructive bronchitis development in bENaC mice.

10 day old new-born bENaC mice and litter mate WT controls were exposed to filtered air (FA) or CS for 50 min twice daily, for 4 days at a particle concentration of 500 mg/m3. Lung function, morphological changes and gene expression were analyzed on day 5.

CS exposed bENaC mice revealed a significant increase in goblet cells (6.39 fold, p < 0.01) and mucus volume (7.2 fold, p < 0.01) compared to CS exposed WT mice. Furthermore, CS exposed bENaC mice showed an increased upregulation of KC (0.06 ± 0.029 vs. 0.02 ± 0.013, p < 0.01), CXCL5 (0.22 ± 0.028 vs. 0.02 ± 0.013, p < 0.01), and GM-CSF (0.1 ± 0.016 vs. 0.05 ± 0.014, p < 0.01) gene expression compared to FA bENaC mice, indicating an elevated inflammatory response. These data were consistent with increased alveolar macrophage cell number and MMP12 mRNA expression (0.17 ± 0.03 vs. 0.08 ± 0.01 CS bENaC vs. CS WT mice respectively). Airspace enlargement revealed no statistical differences in such short term CS exposed bENaC compared to CS exposed WT mice.

We conclude that CS exposure induces a strong inflammatory response and increased mucus production in susceptible newborn mice. This translational study mimics children with obstructive bronchitis suffering from an increased risk of respiratory symptoms and enhanced disease progression in smoking family.

*Presenting author