The Role of Apoptosis in Alveolar Type II and Pulmonary Microvascular Endothelial Cells in the Inflammatory Response After Blunt Chest Trauma

严重的钝性胸部创伤显著改变了局部和全身免疫反应。在挫伤的肺中，多形核中性粒细胞的募集和肺泡巨噬细胞的活化与细胞因子/趋化因子网络一起导致局部炎症反应。已知肺泡II型细胞在肺损伤后的免疫调节过程中发挥重要作用，其通过直接细胞接触或释放的炎症介质进行免疫调节。由于肺泡II型细胞通过调节细胞凋亡来控制表面活性剂的产生和血气屏障上皮部分的再生，因此它们参与肺水肿、肺不张和低氧血症的发展，如在急性呼吸窘迫综合征（ARDS）中所见。在这方面，另一个重要的细胞群是肺微血管内皮，因为其与中性粒细胞和循环介质的相互作用对于创伤后肺部炎症至关重要。肺内皮细胞和肺泡II型细胞的凋亡是该炎症过程中的关键机制。因此，本研究的目的在于阐明双侧肺挫伤后局部炎症反应中这两种细胞类型凋亡的启动子和途径。对于这些实验，使用高度可重复的钝性胸部创伤啮齿动物模型来诱导严重的肺组织创伤。

Severe blunt chest trauma significantly alters the local and systemic immune response. In contused lungs, recruitment of polymorphonuclear neutrophils and activation of alveolar macrophages in concert with the cytokine/chemokine network result in an inflammatory local response. Alveolar Type II cells, which are known to play an important role in immune regulatory processes after lung injury, are immune modulated by direct cellular contact or released inflammatory mediators. Since Alveolar Type II cells control surfactant production and regeneration of the epithelial part of the blood-gas barrier via regulation of apoptosis, they are involved in the development of pulmonary edema, atelectasis and hypoxemia as seen in acute respiratory distress syndrome (ARDS). Another important cell population in this respect is the pulmonary microvascular endothelium as its interaction with neutrophils and circulating mediators is crucial for posttraumatic lung inflammation. Apoptosis of pulmonary endothelial cells and Alveolar Type II cells is a pivotal mechanism in this inflammatory process. Therefore, the project aims to elucidate the initiators and pathways of apoptosis in these two cell types during the local inflammatory response after bilateral lung contusion. For these experiments, a highly reproducible rodent model of blunt chest trauma is used to induce severe pulmonary tissue trauma.