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

钝性胸部创伤可引起局部和全身炎症，并使多名受伤患者的预后恶化。我们发现肺泡2型细胞（AT2）凋亡在挫伤肺中增加。Fas/Fas配体系统似乎至关重要，因为损伤肺肺泡内可溶性Fas配体浓度显著增加，AT2细胞易受Fas配体诱导的凋亡。在接下来的一段时间里，我们希望通过呈递Fas配体来验证巨噬细胞是AT2细胞凋亡的有效诱导剂的假设。我们的研究表明，肺泡巨噬细胞在胸部创伤后被激活，其数量增加。AT2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受伤的肺组织中。与杰克教授，格雷夫斯瓦尔德一起我们将进行实验来验证这一假设。与我们的合作者floh<s:1>博士和Schade教授，Essen一起，我们将确定胸部创伤后树突状细胞的表型变化。关于泛素/蛋白酶体系统改变的后续研究将与迈阿密的Majetschak教授一起进行。与Fandrey教授一起，Essen计划继续研究胸外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.