COMPLEMENT-INDUCED GLOMERULAR EPITHELIAL-CELL INJURY - ROLE OF THE MEMBRANE ATTACK COMPLEX IN RAT MEMBRANOUS NEPHROPATHY
COMPLEMENT-INDUCED GLOMERULAR EPITHELIAL-CELL INJURY - ROLE OF THE MEMBRANE ATTACK COMPLEX IN RAT MEMBRANOUS NEPHROPATHY
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DOI：
10.1172/jci112408
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发表时间：
1986-04-01
影响因子：
15.9
通讯作者：
SALANT, DJ
中科院分区：
文献类型：
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作者：
CYBULSKY, AV;RENNKE, HG;SALANT, DJ
在大鼠被动型Heymann肾炎(PHN)中，抗体(抗Fx1a)与肾小球上皮抗原发生原位反应，并诱导补体(C)介导的细胞非依赖性蛋白尿。为了评估膜攻击复合体(MAC)的作用，我们在PHN的自体阶段模型中确定了C8在蛋白尿发病机制中的必要性。分离的大鼠肾脏，含有非肾炎、非C固定的γ2绵羊抗Fx1a(种植抗原)，当与C固定的豚鼠抗绵羊抗体和C源(新鲜的人血浆50%VOL/VOL在含有牛血清白蛋白的缓冲液中)体外灌流时，20分钟后(0.58.±-)出现明显的蛋白尿。0.08毫克/分。G，n=8)，进一步增加到3.20+-。0.93毫克/分钟。80min后给药。相比之下，注入抗体和热灭活或缺乏C8的人血浆的相同肾脏和注入抗体和新鲜血浆的正常肾脏只排出0.27+-。0.03(n=6)，0.27。+-。0.04(n=5)和0.40.+-。0.05毫克/分。(n=6)20分钟后，0.13±-。0.02，0.22。+-。0.03和0.32。+-。0.05毫克/分。分别于80min后灌胃给药。当C8缺乏的血浆与C8来源重组时(n=3)，蛋白尿恢复到新鲜正常血浆观察到的水平。蛋白质排泄的差异不能用肾小球抗原或抗体含量的数量差异来解释。对肾小球内脏上皮细胞的广泛超微结构损伤仅见于含有抗原的肾脏，这些肾脏灌流抗体和C8-全血浆。因此，在这个模型中，肾小球损伤是由抗原特异性的、抗体导向的、C8依赖的反应引起的，涉及MAC的组装。超微结构的发现支持MAC诱导的肾小球内脏上皮细胞的细胞毒性。
In passive Heymann nephritis (PHN) in rat, antibody (anti-Fx1A) reacts in situ with a glomerular epithelial antigen and induces complement (C)-mediated cell-independent proteinuria. To assess the role of the membrane attack complex (MAC), we determined the need for C8 in the pathogenesis of proteinuria in an autologous-phase model of PHN. Isolated rat kidneys, containing nonnephritogenic, non-C-fixing .gamma.2 sheep anti-Fx1A (planted antigen), when perfused in vitro with C-fixing guinea pig anti-sheep IgG and a source of C (fresh human plasma 50% vol/vol in buffer containing bovine serum albumin), developed marked proteinuria after 20 min (0.58 .+-. 0.08 mg/min .cntdot. g, n = 8) that increased further to 3.20 .+-. 0.93 mg/min .cntdot. g after 80 min. In contrast, identical kidneys perfused with antibody and heat-inactivated or C8-deficient human plasma and normal kidneys perfused with antibody and fresh plasma excreted only 0.27 .+-. 0.03 (n = 6), 0.27 .+-. 0.04 (n = 5), and 0.40 .+-. 0.05 mg/min .cntdot. (n = 6) after 20 min, and 0.13 .+-. 0.02, 0.22 .+-. 0.03, and 0.32 .+-. 0.05 mg/min .cntdot. g after 80 min, respectively. When C8-deficient plasma was reconstituted with sources of C8 (n = 3), proteinuria was restored to the level observed with fresh normal plasma. Differences in protein excretion could not be explained by quantitative differences in glomerular antigen or antibody content. Extensive ultrastructural damage to glomerular visceral epithelial cells was exclusively seen in antigen-containing kidneys perfused with antibody and C8-replete plasma. Thus, glomerular injury in this model results from an antigen-specific, antibody-directed, C8-dependent reaction involving assembly of the MAC. The ultrastructural findings argue in favor of MAC-induced cytotoxicity of the glomerular visceral epithelial cells.