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

II 型肺泡和肺微血管内皮细胞凋亡在胸部钝挫伤后炎症反应中的作用

• 批准号: 5408525
• 负责人: Professor Dr. Markus W. Knöferl
• 金额: --
• 依托单位: Praxisklinik für Orthopädie und Neurochirurgie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5408525?language=en
• 关键词: Role; Apoptosis; Alveolar; Type; II

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.

严重的钝性胸部创伤会显着改变局部和全身的免疫反应。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激活与细胞因子/趋化因子网络协同作用导致局部炎症反应。众所周知，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，通过直接细胞接触或释放的炎症介质进行免疫调节。由于 II 型肺泡细胞通过细胞凋亡的调节控制血气屏障上皮部分的表面活性剂产生和再生，因此它们参与了肺水肿、肺不张和低氧血症的发生，如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，因为它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型细胞的凋亡是这一炎症过程的关键机制。因此，该项目旨在阐明双侧肺挫伤后局部炎症反应过程中这两种细胞类型凋亡的启动因素和途径。在这些实验中，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。