Huen Sarah C, Cantley Lloyd G
Department of Medicine, Section of Nephrology, Yale University, PO Box 208029, New Haven, CT, USA,
Pediatr Nephrol. 2015 Feb;30(2):199-209. doi: 10.1007/s00467-013-2726-y. Epub 2014 Jan 19.
Acute ischemic kidney injury is a common complication in hospitalized patients. No treatment is yet available for augmenting kidney repair or preventing progressive kidney fibrosis. Animal models of acute kidney injury demonstrate that activation of the innate immune system plays a major role in the systemic response to ischemia/reperfusion injury. Macrophage depletion studies suggest that macrophages, key participants in the innate immune response, augment the initial injury after reperfusion but also promote tubular repair and contribute to long-term kidney fibrosis after ischemic injury. The distinct functional outcomes seen following macrophage depletion at different time points after ischemia/reperfusion injury suggest heterogeneity in macrophage activation states. Identifying the pathways that regulate the transitions of macrophage activation is thus critical for understanding the mechanisms that govern both macrophage-mediated injury and repair in the postischemic kidney. This review examines our understanding of the complex and intricately controlled pathways that determine monocyte recruitment, macrophage activation, and macrophage effector functions after renal ischemia/reperfusion injury. Careful delineation of repair and resolution pathways could provide therapeutic targets for the development of effective treatments to offer patients with acute kidney injury.
急性缺血性肾损伤是住院患者常见的并发症。目前尚无促进肾脏修复或预防进行性肾纤维化的治疗方法。急性肾损伤动物模型表明，先天免疫系统的激活在对缺血/再灌注损伤的全身反应中起主要作用。巨噬细胞清除研究表明，巨噬细胞作为先天免疫反应的关键参与者，在再灌注后会加剧初始损伤，但也能促进肾小管修复，并在缺血性损伤后导致长期肾纤维化。在缺血/再灌注损伤后不同时间点进行巨噬细胞清除后观察到的不同功能结果表明巨噬细胞激活状态存在异质性。因此，确定调节巨噬细胞激活转变的途径对于理解缺血后肾脏中巨噬细胞介导的损伤和修复机制至关重要。本综述探讨了我们对决定肾缺血/再灌注损伤后单核细胞募集、巨噬细胞激活和巨噬细胞效应功能的复杂且精细调控途径的理解。仔细描绘修复和消退途径可为开发有效治疗方法提供治疗靶点，从而为急性肾损伤患者提供治疗。
