The pathophysiologic role of Club Cell Protein 16 in the developmentof respiratory complications - Analysis of a clinically relevantcombinatory model of chest trauma and ARDS with special regard tothe function of neutrophil granulocytes
Club Cell 蛋白 16 在呼吸系统并发症发生中的病理生理作用 - 分析胸部创伤和 ARDS 的临床相关组合模型,特别关注中性粒细胞的功能
基本信息
- 批准号:383969007
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2017
- 资助国家:德国
- 起止时间:2016-12-31 至 2018-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The immune response to trauma in patients suffering from a chest/thorax trauma is linked to increased respiratory complications rates, depicting a clinically highly relevant scenario. Hereby, neutrophil granulocytes play a significant role. Initially after trauma the serum levels of Club Cell Protein (CC)16 are significantly increased in trauma patients with lung injuries. This increase may be due to the mechanical cell and tissue injury and a subsequent resulting CC16 release from damaged cells. During this initial, early post-traumatic phase, a compensatory anti-inflammatory response (CARS) is necessary to counterbalance the trauma-induced systemic inflammatory response syndrome (SIRS). However, in this early post-injury phase neutrophil granulocytes get primed, a phenomenon that determines the exaggerated inflammatory response of neutrophils to a delayed secondary trigger. Their exaggerated activation may result in uncontrolled tissue damage, also in the lungs, and thereby may induce the secondary peak of CC16 that was observed in trauma patients with lung injury suffering from pneumonia. The pathophysiologic relevance of this secondary CC16 increase in serum from trauma patients with lung injury and respiratory complications remains unclear. Therefore, the aim of the present study is to characterize the influence of a) locally released CC16 (lungs, BAL-F) as well as b) systemic CC16 (serum) levels on the functionality of neutrophil granulocytes including the evaluation of involved mechanisms. This data may open new windows for potential therapy options within these clinical settings. Therefore, in this study, we intent to evaluate the influence of the initially (directly, early) after trauma and delayed (days after trauma) released CC16 on the neutrophil functionality (phagocytosis, apoptosis, oxidative burst, migration, maturation), the systemic as well as local inflammatory reaction, organ/tissue injury after major (poly) trauma in a porcine model. The influence of CC16 on neutrophil granulocytes may increase the vulnerability for clinical infections in this model including lung injury. Additionally, in in vivo experiments, the impact of both, local and systemic application ofCC16-neutralizing antibodies, either initially after trauma or later on, on the local and systemic inflammatory reaction, organ function and survival will be evaluated.
胸/胸外伤患者对创伤的免疫反应与呼吸系统并发症发生率增加有关,这在临床上具有高度相关性。因此,中性粒细胞起着重要的作用。创伤后肺损伤患者血清俱乐部细胞蛋白(CC)16水平显著升高。这种增加可能是由于机械细胞和组织损伤以及随后导致受损细胞释放CC16。在最初的创伤后早期阶段,代偿性抗炎反应(CARS)是平衡创伤诱导的全身炎症反应综合征(SIRS)所必需的。然而,在损伤后的早期阶段,中性粒细胞被启动,这一现象决定了中性粒细胞对延迟的继发性触发的夸大炎症反应。它们的过度激活可能导致不受控制的组织损伤,也可能发生在肺部,从而可能诱发CC16的二次峰值,这在肺部损伤合并肺炎的创伤患者中观察到。伴有肺损伤和呼吸系统并发症的创伤患者血清中继发性CC16升高的病理生理学相关性尚不清楚。因此,本研究的目的是表征a)局部释放的CC16(肺,BAL-F)以及b)全身CC16(血清)水平对中性粒细胞功能的影响,包括对相关机制的评估。这些数据可能为这些临床环境中的潜在治疗选择打开新的窗口。因此,在本研究中,我们打算评估创伤后最初(直接、早期)和延迟(创伤后几天)释放CC16对猪模型中中性粒细胞功能(吞噬、凋亡、氧化破裂、迁移、成熟)、全身和局部炎症反应、重大(多重)创伤后器官/组织损伤的影响。CC16对中性粒细胞的影响可能会增加该模型临床感染的易感性,包括肺损伤。此外,在体内实验中,将评估局部和全身应用cc16中和抗体(创伤后或之后)对局部和全身炎症反应、器官功能和生存的影响。
项目成果
期刊论文数量(0)
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Professor Dr. Frank Hildebrand其他文献
Professor Dr. Frank Hildebrand的其他文献
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{{ truncateString('Professor Dr. Frank Hildebrand', 18)}}的其他基金
Differential surgical and immunological control in a long-term pig polytrauma model
长期猪多发伤模型中的差异化手术和免疫控制
- 批准号:
429837092 - 财政年份:2020
- 资助金额:
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Characteristics of extracellular vesicles and their potential role in organ-cross talk after multiple trauma
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495572674 - 财政年份:
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