MACROPHAGE EMIGRATION FROM THE INFLAMED KIDNEY INTERSTITIUM: REGULATION BY APOPTOTIC CELLS

肾脏的炎症是一种严重的疾病，即使采用传统的药物治疗，也会导致肾脏瘢痕形成和肾衰竭，因此需要进行透析或肾移植。巨噬细胞是一种在炎症过程中起关键作用的白色血细胞，大量证据表明巨噬细胞参与进行性肾脏炎症。巨噬细胞浸润在缓解炎症中是短暂的，并且有证据表明巨噬细胞可以通过淋巴系统离开发炎部位并运输到淋巴结。死亡细胞存在于发炎和愈合的组织中，是巨噬细胞的重要刺激物。事实上，巨噬细胞对垂死细胞的摄取促进了促进炎症消退的抗炎介质的产生。我们的工作表明，将死亡细胞滴注到腹腔中会引导驻留的或炎性的腹腔巨噬细胞离开腹腔并迁移到引流淋巴结。此外，我们有证据表明巨噬细胞上的一种特殊受体参与了这一过程。在这个建议中，我们将确定在发炎和愈合的肾脏内的死亡细胞是否可以类似地引导巨噬细胞从肾脏中迁移，并剖析潜在的机制。这项工作可能使我们能够产生新的方法，通过促进有害巨噬细胞从发炎的肾脏中迁移来抑制患者的肾脏炎症。

Inflammation of the kidneys is a serious condition and, even with conventional medical treatment, can lead to kidney scarring and kidney failure such that dialysis or a kidney transplant is required. The macrophage is a white blood cell that plays a key role in inflammatory processes and a body of evidence implicates the macrophage in progressive renal inflammation. Macrophage infiltration in resolving inflammation is transient and evidence suggests that macrophages may leave inflamed sites via the lymphatic system and traffic to lymph nodes. Dying cells are present within inflamed and healing tissues and are an important stimulus for macrophages. Indeed, the ingestion of dying cells by macrophages promotes the generation of anti-inflammatory mediators that facilitate the resolution of inflammation. Our work indicates that the instillation of dying cells into the abdomen directs resident or inflammatory peritoneal macrophages to exit the abdomen and emigrate to the draining lymph nodes. Furthermore, we have evidence implicating a particular receptor on the macrophage in this process. In this proposal we shall determine whether dying cells within the inflamed and healing kidney may similarly direct macrophages to emigrate from the kidney and dissect the underlying mechanism. This work may allow us to generate new ways to dampen down kidney inflammation in patients by promoting the emigration of injurious macrophages from the inflamed kidney.