The role, interplay and phenotypic changes of platelets in inflammation mediated organ damage.

血小板在炎症介导的器官损伤中的作用、相互作用和表型变化。

• 批准号: 460682455
• 负责人: Dr. Andreas Margraf
• 金额: --
• 依托单位: Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie
• 依托单位国家: 德国
• 项目类别: WBP Fellowship
• 财政年份: 2021
• 资助国家: 德国
• 起止时间: 2020-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/460682455?language=en
• 关键词: role; interplay; phenotypic; changes; platelets

A well-balanced inflammatory reaction allows the body to defend itself against external pathogens, whereas an overshooting inflammatory response can harm the organism itself. Such uncontrolled inflammatory response can be observed in septic patients and to a lesser extent also in arthritis patients. Herein, the recruitment and unhindered activation of inflammatory cells and breaking of the endothelial barrier lead to not only local inflammatory complications, such as edema formation or joint destruction, but due to a systemic overshooting inflammatory response also to secondary (remote) organ damage. Importantly, any inflammatory response must be terminated and resolved to prevent ongoing organ damage. Platelets have been found to affect acute onset of arthritis as well as acute lung injury, but little is known about the resolution potential of platelets, changes in platelet and macrophage phenotypes, impact of such on recruitment of inflammatory cells and the role of platelet-microparticles in mediation of secondary organ dysfunction. Interestingly, platelet-microparticles have been found to directly mediate local inflammation but dissemination of platelet-microparticles to remote regions within the body has also been discovered, detecting these particles in lymph and bone marrow during arthritis. This project aims to elucidate underlying mechanisms of platelet-mediated inflammation and resolution of inflammatory processes as well as the impact of microparticles on secondary organ damage, inflammation, and resolution. Of special interest, interplay of platelets with macrophages, which are known to be main contributors to both inflammation and cell-clearance during resolution, and phenotypic changes will be examined in different disease models and organs. As inflammatory conditions such as arthritis, colitis and sepsis are common clinical morbidities resulting in high hospital expenditures and mortality rates, advancing the understanding of regulatory mechanisms of inflammation, secondary organ damage and resolution of such is of utmost importance for translational endeavors.

平衡良好的炎症反应使身体能够抵御外部病原体，而过度的炎症反应可能会伤害生物体本身。这种不受控制的炎症反应可以在脓毒症患者中观察到，并且在关节炎患者中也可以观察到程度较低。在本文中，炎性细胞的募集和不受阻碍的活化以及内皮屏障的破坏不仅导致局部炎性并发症，例如水肿形成或关节破坏，而且由于全身性过度炎症反应也导致继发性（远程）器官损伤。重要的是，任何炎症反应必须终止和解决，以防止持续的器官损伤。已发现血小板减少影响关节炎的急性发作以及急性肺损伤，但对血小板的溶解潜力、血小板和巨噬细胞表型的变化、其对炎性细胞募集的影响以及血小板微粒在介导继发性器官功能障碍中的作用知之甚少。有趣的是，已发现血小板微粒直接介导局部炎症，但也发现血小板微粒向体内偏远区域的传播，在关节炎期间在淋巴和骨髓中检测到这些颗粒。该项目旨在阐明血小板介导的炎症和炎症过程的消退的潜在机制，以及微粒对继发性器官损伤，炎症和消退的影响。特别感兴趣的是，血小板与巨噬细胞的相互作用，这是已知的炎症和细胞清除过程中的主要贡献者，以及表型变化将在不同的疾病模型和器官中进行检查。由于炎性病症如关节炎、结肠炎和败血症是导致高医院支出和死亡率的常见临床发病率，因此推进对炎症、继发性器官损伤的调节机制的理解以及这些的解决对于翻译工作至关重要。