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

钝性胸部创伤引起局部和全身炎症，并使多发伤患者的预后恶化。我们确定，肺泡2型细胞（AT 2）凋亡增加挫伤肺。Fas/Fas配体系统似乎是至关重要的参与作为浓度的可溶性Fas配体显着增加intraalveolarly在创伤性肺和AT 2细胞容易Fas配体诱导的凋亡。在接下来的时间里，我们希望测试的假设，即巨噬细胞是有效的诱导凋亡的AT 2细胞通过提供Fas配体。我们的研究表明，肺泡巨噬细胞被激活，它们的数量增加后胸部创伤。AT 2细胞对肺挫伤的反应是增加趋化介质的释放。我们的假设是钝性胸部创伤导致血液单核细胞迁移到创伤的肺组织中。我们将与杰克教授一起进行实验来验证这一假设。与我们的合作者Flohé博士和Schade，埃森教授一起，我们将确定胸部创伤后树突状细胞的表型变化。将与Majetschak教授（迈阿密）一起进行关于泛素/蛋白酶体系统改变的随访研究。埃森与Fanjun教授一起计划继续研究胸部创伤后肺泡巨噬细胞中缺氧诱导因子1的减少。

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.