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

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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.