Lung inflammatory response to blut chest trauma - role of monocyte transmigration, macrophage induced alveolar type 2 cell apoptosis and dendritic cell function

• Applicant: Professor Dr. Markus W. Knöferl
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2007 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 68338991

Blunt chest trauma induces local and systemic inflammation and deteriorates outcome in multiple injured patients. We determined that alveolar type 2 cell (AT2) apoptosis is increased in contused lungs. The Fas/Fas ligand system appears to be critically involved as concentrations of soluble Fas ligand were significantly increased intraalveolarly in traumatized lungs and AT2 cells were susceptible to Fas ligand induced apoptosis. In the next period we wish to test the hypothesis that macrophages are potent inducers of apoptosis in AT2 cells by presenting Fas ligand. Our studies have shown that alveolar macrophages are activated and that their number increases after chest trauma. AT2 cells respond to lung contusion with increased release of chemotactic mediators. Our hypothesis is that blunt chest trauma causes blood monocytes to migrate into traumatized lung tissue. Together with Professor Jack, Greifswald we will carry out experiments to test this hypothesis. With our collaborators Dr. Flohé and Prof. Schade, Essen we will determine phenotypic changes of dendritic cells following chest trauma. Follow up studies concerning alterations of the ubiquitin/proteasome system will be conducted with Prof. Majetschak, Miami. Together with Prof. Fandrey, Essen continuing studies are planned regarding the decrease of hypoxia inducible factor 1 in alveolar macrophages after chest trauma.

• DFG Programme: Research Grants
• Participating Person: Dr. Daniel Heiko Seitz