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Wednesday, 16.09.2009
Mechanisms of infection: what's new?
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Interplay between bacterial infections, hypoxia and the development of chronic lung diseases
S. Osbahr, D. Droemann, K. Dalhoff, J. Rupp (Lübeck, Germany)
Source:
Annual Congress 2009 - Mechanisms of infection: what's new?
Session:
Mechanisms of infection: what's new?
Session type:
E-Communication Session
Number:
4788
Disease area:
Respiratory infections
Abstract
Inadequate epithelial repair mechanisms and dysbalanced epithelial to mesenchymal cell transitions (EMT) are supposed to be key factors in the development of chronic damages in the lung architecture. We wondered whether the infection of alveolar epithelial cells (A549) with H. influenzae (Hi) and C. pneumoniae (Cp) induces vasoactive and growth factors with known effects on airway remodelling. We further wanted to know whether hypoxia, as a consequence of reduced ventilation of the small airways during pneumonia, might potentiate the release of these factors. In first experiments we could show that Hi-induced expression of VEGF and Endothelin-1 (ET-1) in A549 cells significantly increased under hypoxic conditions (8.6-fold ± 4.0 vs. 1.7-fold ± 0.4; 2.4-fold ± 1.0 vs. 1.4-fold ± 0.5, respectively). Similar results for VEGF but not for ET-1 were observed in Cp infected A549 cells. Using siRNA against the hypoxia-inducible factor-1 (HIF-1α) we could almost completely block bacteria induced VEGF and ET-1 expression under hypoxia. Interestingly, infection of A549 cells with Hi or Cp had no impact on the expression of TGF-β, which is the so far best described mediator of EMT in lung tissue. Taken together our data indicate that respiratory pathogens at least in acute infections with local tissue inflammation and increased oxygen consumption induce vasoactive and growth factors in lung epithelial cells and alveoalar macrophages (data not shown). Further studies using the human lung tissue culture model and primary alveolar epithalial cells are needed to elucidate the role of these factors for the remodelling of lung tissue.
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Citations should be made in the following way:
S. Osbahr, D. Droemann, K. Dalhoff, J. Rupp (Lübeck, Germany). Interplay between bacterial infections, hypoxia and the development of chronic lung diseases. Eur Respir J 2009; 34: Suppl. 53, 4788
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