School of Medicine, University of Belgrade, Belgrade, Serbia.
Clinic for Nephrology, Clinical Center of Serbia, Belgrade, Serbia.
J Immunol Res. 2017;2017:6305439. doi: 10.1155/2017/6305439. Epub 2017 Jun 6.
Acute kidney injury caused by ischemia and subsequent reperfusion is associated with a high rate of mortality and morbidity. Ischemia/reperfusion injury in kidney transplantation causes delayed graft function and is associated with more frequent episodes of acute rejection and progression to chronic allograft nephropathy. Alloantigen-independent inflammation is an important process, participating in pathogenesis of injurious response, caused by ischemia and reperfusion. This innate immune response is characterized by the activity of classical cells belonging to the immune system, such as neutrophils, macrophages, dendritic cells, lymphocytes, and also tubular epithelial cells and endothelial cells. These immune cells not only participate in inflammation after ischemia exerting detrimental influence but also play a protective role in the healing response from ischemia/reperfusion injury. Delineating of complex mechanisms of their actions could be fruitful in future prevention and treatment of ischemia/reperfusion injury. Among numerous so far conducted experiments, observed immunomodulatory role of adenosine and adenosine receptor agonists in complex interactions of dendritic cells, natural killer T cells, and T regulatory cells is emphasized as promising in the treatment of kidney ischemia/reperfusion injury. Potential pharmacological approaches which decrease NF-B activity and antagonize mechanisms downstream of activated Toll-like receptors are discussed.
缺血和随后的再灌注引起的急性肾损伤与高死亡率和发病率有关。肾移植中的缺血/再灌注损伤导致移植物功能延迟，并与更频繁的急性排斥反应发作和进展为慢性同种异体移植肾病有关。同种异体抗原非依赖性炎症是一个重要的过程，参与缺血和再灌注引起的损伤反应的发病机制。这种先天免疫反应的特点是免疫系统的经典细胞（如中性粒细胞、巨噬细胞、树突状细胞、淋巴细胞）的活性，以及肾小管上皮细胞和内皮细胞。这些免疫细胞不仅在缺血后炎症中发挥有害作用，而且在缺血/再灌注损伤的愈合反应中发挥保护作用。阐明它们作用的复杂机制在未来预防和治疗缺血/再灌注损伤方面可能是富有成效的。在迄今为止进行的众多实验中，强调了腺苷和腺苷受体激动剂在树突状细胞、自然杀伤 T 细胞和 T 调节细胞的复杂相互作用中观察到的免疫调节作用，这在治疗肾缺血/再灌注损伤方面具有很大的应用前景。还讨论了降低 NF-B 活性和拮抗激活的 Toll 样受体下游机制的潜在药物治疗方法。
