Therapeutic treatment with Ang-1 reduced lung permeability and neutrophil recruitment in pneumonia-affected mice, highlighting the Ang-/Tie2-system's therapeutic potential.
Does Ang-1 treatment or Ang-2 inhibition reduce inflammation and lung permeability in pneumococcal pneumonia?
The Ang-/Tie2-system plays a central role in pneumonia-evoked inflammation and permeability, suggesting Ang-1 supplementation or Ang-2 inhibition as potential therapies for severe pneumonia.
Absolute Event Rate: 0% vs 0%
In pneumonia, pathogen-host interaction may evoke pulmonary endothelial permeability despite efficient antimicrobial therapy, resulting in life-threatening lung failure. Angiopoietin (Ang)-1 mediated Tie2-activation reduces and the Ang-1 antagonist Ang-2 increases inflammation and endothelial permeability in sepsis, but the role of the Ang-/Tie2-system in pneumonia has not been examined. Serum samples of pneumonia patients, human lung tissue (post mortem), lungs of S. pneumoniae infected mice, pneumolysin-stimulated isolated perfused and ventilated mouse lungs and human microvascular endothelial cells (HMVEC) were investigated. We observed decreased Ang-1 and increased Ang-2 serum levels in pneumonia patients. Immunohistochemistry staining of human lung tissue revealed that Ang-2 was exclusively expressed in endothelial cells, whereas Ang-1 was expressed in different cell types. In HMVEC, mRNA expression of Ang-1 and Tie2 was decreased after pneumolysin stimulation, and Ang-2 expression was increased. Further, we detected reduced pulmonary mRNA expression of Ang-1 and Tie2 and increased Ang-2 expression in murine lung tissue following in vivo infection with S. pneumoniae . Therapeutic treatment with Ang-1 reduced neutrophil recruitment, inflammatory cytokines in bronchoalveolar lavage and lung permeability in pneumonic mice. When mice were pretreated with siRNA (Atuplex), pneumolysin-evoked permeability in isolated perfused lungs of siRNA Ang-2 pretreated mice was reduced as compared to lungs of control mice. These results suggest a central role of the Ang-/Tie2-system in pneumonia-evoked inflammation and permeability, and provide a new therapeutic perspective for severe pneumonia.
Gutbier et al. (Thu,) reported a other. Therapeutic treatment with Ang-1 reduced lung permeability and neutrophil recruitment in pneumonia-affected mice, highlighting the Ang-/Tie2-system's therapeutic potential.