Complement regulation in renal disease models.
Complement regulation in renal disease models.
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DOI：
10.1016/j.semnephrol.2013.08.008
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发表时间：
2013-11
影响因子：
3.3
通讯作者：
Quigg, Richard J.
中科院分区：
文献类型：
--
作者：
Naik, Abhijit;Sharma, Shweta;Quigg, Richard J.
补体系统的激活受到血浆和细胞相关补体调节蛋白（CRPs）的严格调控，如H因子（fH）、衰变加速因子（DAF）和膜辅助因子蛋白（MCP）。疾病的动物模型为CRPs在肾脏中的重要作用提供了相当多的见解。fH缺乏的小鼠有过多的流体相C3激活和失活，导致iC3b在肾小球毛细血管壁（GCW）沉积，类似于致密沉积病。相反，当fH缺乏c端表面靶向区域时，GCW的局部激活会导致类似血栓性微血管病的疾病。独特的啮齿动物蛋白，cr1相关的y (Crry)，具有类似于人类MCP的特征。有缺陷的哭泣导致小管间质（TI）不受限制的替代途径激活，导致TMA、急性肾损伤和TI肾炎等病理特征。在经典或凝集素途径的启动物存在的情况下，通常以人类肾小球疾病中免疫复合物的形式存在，补体对自身的调节受到强调，有可能招募自发活跃的替代途径。这种激活的阈值是由crp设定的；当补体调节有缺陷时，病理更可能发生。在GCW的毛细血管内区域，fH是关键，而DAF和Crry对系膜细胞和足细胞具有保护作用。可以说，这些CRPs的获得性改变是一种更常见的事件，从细胞损伤的病理状态或抑制性抗体的产生，延伸到适应性免疫反应的生理微调。
Activation of the complement system is tightly regulated by plasma and cell-associated complement regulatory proteins (CRPs), such as factor H (fH), decay-accelerating factor (DAF), and membrane cofactor protein (MCP). Animal models of disease have provided considerable insights into the important roles for CRPs in the kidney. Mice deficient in fH have excessive fluid phase C3 activation and inactivation leading to deposition of iC3b in glomerular capillary walls (GCW), comparable to dense deposit disease. In contrast, when fH lacks C-terminal surface targeting regions, local activation on the GCW leads to a disease reminiscent of thrombotic microangiopathy. The uniquely rodent protein, CR1-related y (Crry), has features analogous to human MCP. Defective Crry leads to unrestricted alternative pathway activation in the tubulointerstitium (TI) resulting in pathological features ranging from TMA, acute kidney injury and TI nephritis. In the presence of initiators of the classical or lectin pathways, commonly in the form of immune complexes in human glomerular diseases, complement regulation on self is stressed, with the potential for recruitment of the spontaneously active alternative pathway. The threshold for this activation is set by CRPs; pathology is more likely when complement regulation is defective. Within the endocapillary region of the GCW, fH is key, while DAF and Crry are protective on mesangial cells and podocytes. Arguably, acquired alterations in these CRPs is a more common event, extending from pathological states of cellular injury or production of inhibitory antibodies, to physiological fine tuning of the adaptive immune response.
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影响因子：
5
作者：
Bao, Lihua;Haas, Mark;Quigg, Richard J.
通讯作者：
Quigg, Richard J.
影响因子：
13.6
作者：
Bao, Lihua;Wang, Ying;Quigg, Richard J.
通讯作者：
Quigg, Richard J.
影响因子：
19.6
作者：
Bao, Lihua;Wang, Ying;Quigg, Richard J.
通讯作者：
Quigg, Richard J.
DOI：
10.1073/pnas.69.10.2910
发表时间：
1972-01-01
影响因子：
11.1
作者：
ALPER, CA;ROSEN, FS;LACHMANN, PJ
通讯作者：
LACHMANN, PJ
影响因子：
13.6
作者：
Alexander, JJ;Pickering, MC;Quigg, RJ
通讯作者：
Quigg, RJ