Pneumologie 2015; 69 - A28
DOI: 10.1055/s-0035-1556620

Pulmonary allergen clearance is impaired by airway surface dehydration

M Hagner 1, S Schmidt 1, E Maier 1, S Christochowitz 1, M Lampe 2, MA Mall 1, B Fritzsching 1
  • 1Department of Translational Pulmonology, Translational Lung Research Center (TLRC), Member of the German Center of Lung Research (DZL), University of Heidelberg, Germany
  • 2European Molecular Laboratory (EMBL), Heidelberg, Germany

Introduction: Efficient clearance of inhaled allergens from the lungs of patients with allergic asthma is important to avoid prolonged allergen exposure and asthma exacerbation. We hypothesized that impaired mucociliary clearance constitutes a risk factor for inefficient intrapulmonary allergen clearance. Thus, we analyzed allergen clearance mechanisms in wild type (WT) mice and in mice with airway-specific overexpression of the sodium channel ENaC (βENaC-Tg), which suffer from airway surface dehydration, impaired mucociliary clearance and chronic airway inflammation (Mall et al., Nat Med., 2004).

Methods: Mucociliary clearance was determined by intratracheal application of 1 µm fluorescent beads and video-microscopic analysis of in vivo bead elimination. Following intrapulmonary application of fluorescently labeled Aspergillus fumigatus extract (Af), total allergen clearance was analyzed by measurement of residual fluorescence in lung homogenates after designated time points. Bronchoalveolar lavage (BAL) from WT and βENaC-Tg mice was analyzed by flow cytometry to identify immune cell populations with Af uptake.

Results: Mucociliary clearance and total lung allergen clearance were significantly reduced in βENaC-Tg mice compared to WT mice. Antigen-presenting cells including alveolar macrophages (AM) and conventional dendritic cells (cDCs) were identified as cell types with strongest Af uptake among immune airway cells. In addition to decreased total allergen clearance, βENaC-Tg mice showed reduced allergen uptake by AM when compared to WT mice. However, the level of allergen presenting airway cDCs was significantly elevated in βENaC-Tg mice.

Conclusion: We conclude that airway surface dehydration impairs pulmonary allergen clearance. Hence, we suggest that inefficient allergen clearance might contribute to increased allergen presentation by cDCs which could constitute a risk factor for allergic sensitization during chronic airway inflammation.

*Presenting author