Increased urinary excretion of C5b-9 distinguishes passive Heymann nephritis in the rat.
Increased urinary excretion of C5b-9 distinguishes passive Heymann nephritis in the rat.
复制标题
C5b-9 尿排泄增加可区分大鼠被动海曼肾炎。
DOI：
10.1038/ki.1989.8
复制
发表时间：
1989
影响因子：
19.6
通讯作者：
Couser,WG
中科院分区：
文献类型：
--
作者：
Schulze,M;Baker,PJ;Perkinson,DT;Johnson,RJ;Ochi,RF;Stahl,RA;Couser,WG
尿中C5b-9的增加是大鼠被动海曼肾炎的特征。尿中C5b-9的增加将被动海曼肾炎与其他形式的实验性肾小球肾炎区分开来。在被动海曼肾炎（PHN）的膜性肾病（MN）模型中，抗fx1a抗体与肾小球上皮细胞膜上表达的抗原反应，随后膜补丁和免疫复合物脱落，形成上皮下沉积。免疫复合物沉积伴随着C5b-9的沉积，这是介导蛋白尿所必需的。我们检验了一种假设，即上皮细胞膜上的C5b-9组装可能导致C5b-9在尿液中排泄，这将区分MN的这种自身免疫机制与导致上皮下免疫复合物沉积的其他过程。使用针对大鼠C6和大鼠C5b-9新抗原的单克隆抗体，在敏感的ELISA检测中，大鼠尿中C5b-9的排泄量升高与肾小球免疫沉积形成相关。在外源性抗原（阳性IgG）诱导的MN中，尽管肾小球中有相当的C5b-9沉积，或在肾毒性肾炎、内皮下免疫复合物肾炎、抗系膜抗体诱导的肾炎或两种非免疫性肾病模型中，未检测到尿C5b-9。在蛋白尿动物中输注预先形成的C5b-9，排除了C5b-9的肾小球滤过作为尿中C5b-9排泄的促进机制。我们得出结论，在大鼠中，尿中C5b-9的增加是肾小球上皮细胞抗原抗体诱导的MN的标志。尿C5b-9的排泄反映了活跃的肾小球免疫沉积的形成，并将该机制诱导的MN与其他形式的MN以及其他具有等效肾小球C5b-9沉积的肾小球疾病区分开来。
Increased urinary excretion of C5b-9 distinguishes passive Heymann nephritis in the rat. Increased urinary excretion of C5b-9 distinguishes passive Heymann nephritis from other forms of experimental glomerulonephritis in the rat. In the passive Heymann nephritis (PHN) model of membranous nephropathy (MN) subepithelial deposits form from anti-Fx1A antibody reacting with antigen expressed on the glomerular epithelial cell membrane followed by membrane patching and shedding of immune complexes. Immune complex deposits are accompanied by deposits of C5b-9 which is required for the mediation of proteinuria. We tested the hypothesis that C5b-9 assembly on the epithelial cell membrane might result in C5b-9 excretion in the urine, which would distinguish this autoimmune mechanism of MN from other processes that result in subepithelial immune complex deposits. Using monoclonal antibodies developed to rat C6 and a rat C5b-9 neoantigen, in a sensitive ELISA assay, elevated urinary excretion of rat C5b-9 was documented in PHN associated with on-going glomerular immune deposit formation. No urinary C5b-9 was detectable in MN induced by an exogenous antigen (cationized IgG) despite equivalent glomerular C5b-9 deposits, or in models of nephrotoxic nephritis, subendothelial immune complex nephritis, anti-mesangial cell membrane antibody-induced nephritis or two non-immune nephropathies. Infusion of preformed C5b-9 in proteinuric animals excluded glomerular filtration of C5b-9 as a contributing mechanism to urinary C5b-9 excretion. We conclude that in the rat, increased urinary excretion of C5b-9 is a marker of MN induced by antibody to a glomerular epithelial cell antigen. Urine C5b-9 excretion reflects active glomerular immune deposit formation and distinguishes MN induced by this mechanism from other forms of MN as well as from other glomerular diseases with equivalent glomerular C5b-9 deposits.