Pneumologie 2015; 69 - P04
DOI: 10.1055/s-0035-1551906

Cigarette smoke exposure enhances obstructive bronchitis in ENaC overexpressing newborn-mice

J Jia 1, TM Conlon 1, C Ballester Lopez 1, O Eickelberg 1, 2, MA Mall 3, AÖ Yildirim 1
  • 1Comprehensive Pneumology Center (CPC), Institute of Lung Biology and Disease, Helmholtz Zentrum, German Center for Lung Research (DZL), Munich, Germany
  • 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 airflow limitation, airway remodeling and respiratory obstruction. Overexpression of Na+ ion channels (βENaC) 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 exposure is recognized to be 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 βENaC mice.

10 day old new-born βENaC mice and litter mate WT controls were exposed to filtered air (FA) or cigarette smoke (CS) for 50 min twice daily, for 4 days at a particle concentration of 500 mg/m3. Lung function, mucus production, morphological changes and gene expression were analyzed on day 5. Differential cell counts were analyzed by sampling bronchoalveolar lavage fluid.

CS exposed βENaC 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 βENaC 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 βENaC 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 βENaC vs. CS WT mice respectively). Conversely, airspace enlargement revealed no statistical differences in such short term CS exposed βENaC 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 a smoking family.