Division of Nephrology, Medizinische Klinik und Poliklinik IV, Campus Innenstadt, University of Munich-LMU, Munich, Germany.
Kidney Int. 2013 Apr;83(4):647-61. doi: 10.1038/ki.2012.463. Epub 2013 Jan 16.
Ischemia-reperfusion activates innate immunity and sterile inflammation, resulting in acute kidney injury. Since pentraxin 3 (PTX3) regulates multiple aspects of innate immunity and tissue inflammation, we tested whether PTX3 would be involved in renal ischemia-reperfusion injury. Renal pedicle clamping increased PTX3 serum levels, as well as PTX3 expression, inside the kidney but predominantly in CD45/CD11c(+) cells, a subpopulation of intrarenal mononuclear phagocytes. Lack of PTX3 aggravated postischemic acute kidney injury as evidenced by massive tubular necrosis, and TNF and IL-6 release, as well as massively increased neutrophil and macrophage infiltrates at 24 h. This was followed by tubular atrophy, interstitial fibrosis, and kidney shrinking 10 weeks later. In vivo microscopy uncovered increased leukocyte adhesion and transmigration in postischemic microvessels of Ptx3-deficient mice. Furthermore, injection of recombinant PTX3 up to 6 h after reperfusion prevented renal leukocyte recruitment and postischemic kidney injury. Thus, local PTX3 release from a subpopulation of intrarenal mononuclear phagocytes or delayed PTX3 treatment limits postischemic renal inflammation. Conversely, Ptx3 loss-of-function mutations predispose to postischemic acute kidney injury and subsequent chronic kidney disease.
缺血再灌注激活固有免疫和无菌性炎症，导致急性肾损伤。由于五聚素 3（PTX3）调节固有免疫和组织炎症的多个方面，我们测试了 PTX3 是否参与肾缺血再灌注损伤。肾蒂夹闭增加了血清 PTX3 水平以及肾脏内 PTX3 的表达，但主要在 CD45/CD11c(+)细胞（肾内单核吞噬细胞的一个亚群）中。缺乏 PTX3 加重了缺血后急性肾损伤，表现为大量肾小管坏死和 TNF 和 IL-6 释放，以及 24 小时时大量中性粒细胞和巨噬细胞浸润。随后出现肾小管萎缩、间质纤维化和 10 周后肾脏缩小。体内显微镜检查显示，缺血后 Ptx3 缺陷小鼠的微血管中白细胞黏附和迁移增加。此外，再灌注后 6 小时内注射重组 PTX3 可防止肾白细胞募集和缺血后肾损伤。因此，局部 PTX3 从肾内单核吞噬细胞的一个亚群释放或延迟的 PTX3 治疗限制了缺血后的肾脏炎症。相反，Ptx3 功能丧失突变易导致缺血后急性肾损伤和随后的慢性肾脏病。
