Liew Pei Xiong
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Am J Physiol Cell Physiol. 2021 Aug 1;321(2):C384-C393. doi: 10.1152/ajpcell.00429.2020. Epub 2021 Jul 7.
Inflammation of the kidney is a key contributor to proliferative glomerulonephritis, and kidney damage during glomerulonephritis can lead to renal failure. The immune response associated with glomerulonephritis episodes is a major determinant of patient outcomes, and understanding this response is paramount for effective therapeutic treatment. Neutrophils are the first responders to sites of infection or tissue injury and are a significant cellular infiltrate during proliferative glomerulonephritis. This immune cell was initially recognized as a "blunt" nonspecific effector cell that was recruited to kill pathogens and then die quickly. However, recent studies have shown that the behavior and function of neutrophils are substantially more complex. Neutrophil recruitment to inflammatory sites must be carefully regulated so that these potent cells accurately arrive at tissue sites and perform their functions without nonspecific injury to other locations. As the kidney contains unique microvasculature befitting their specialized role in blood filtration, the recruitment of neutrophils in the renal environment differs from other organs. This Mini-Review will describe how advances in live-animal (intravital) imaging led to the discovery of novel recruitment pathways in the kidney, particularly in the glomeruli, and highlight these differences to canonical neutrophil recruitment. In addition, molecular engagement of surface molecules that lead to intracellular signaling, which is followed by neutrophil capture in the glomeruli, is also briefly discussed. Finally, the contribution of other immune cells in renal neutrophil recruitment, the fate of the emigrated neutrophils after inflammation, and the relevance of mouse models compared with human glomerulonephritides will also be explored.
肾脏炎症是增殖性肾小球肾炎的关键促成因素,而肾小球肾炎期间的肾脏损伤可导致肾衰竭。与肾小球肾炎发作相关的免疫反应是患者预后的主要决定因素,了解这种反应对于有效的治疗至关重要。中性粒细胞是感染或组织损伤部位的首批应答者,也是增殖性肾小球肾炎期间显著的细胞浸润成分。这种免疫细胞最初被认为是一种“钝性”非特异性效应细胞,被募集来杀死病原体,然后迅速死亡。然而,最近的研究表明,中性粒细胞的行为和功能要复杂得多。必须仔细调节中性粒细胞向炎症部位的募集,以便这些强大的细胞准确到达组织部位并发挥其功能,而不会对其他部位造成非特异性损伤。由于肾脏含有独特的微血管,适合其在血液滤过中的特殊作用,因此肾脏环境中中性粒细胞的募集与其他器官不同。本综述将描述活体动物(体内)成像技术的进展如何促成了肾脏中,特别是肾小球中新的募集途径的发现,并强调这些与经典中性粒细胞募集的差异。此外,还将简要讨论导致细胞内信号传导的表面分子的分子结合,随后中性粒细胞在肾小球中的捕获。最后,还将探讨其他免疫细胞在肾脏中性粒细胞募集中的作用、炎症后迁移出的中性粒细胞的命运,以及小鼠模型与人类肾小球肾炎的相关性。