Cybulsky A V, Quigg R J, Salant D J
J Immunol. 1986 Sep 1;137(5):1511-6.
Using a model of rat membranous nephropathy (MN), we examined the relationship between the development of glomerular epithelial cell injury and the formation and stability of the membrane attack complex (MAC) of complement. Isolated rat kidneys were perfused with buffered bovine albumin (BSA) or various plasmas (complement source). Kidneys containing nephritogenic amounts of complement-fixing sheep antibody to glomerular epithelial antigens (aFx1A) perfused with BSA (n = 5), and normal kidneys perfused with normal human plasma in BSA (50% v/v, n = 6) excreted 0.30 +/- 0.02 mg protein/min/g during 90 min perfusion (control groups). When normal plasma was added to the perfusate of aFx1A kidneys at concentrations of 12.5, 25, and 50% v/v, protein excretion rose in a time- and concentration-dependent manner. Perfusions with 25% plasma resulted in baseline proteinuria from 0 to 20 min that increased to 2.8 +/- 0.9 mg/min/g at 20 to 40 min and 8.6 +/- 2.1 at 40 to 60 min (n = 4, p less than 0.01 vs control groups). Removal of plasma at 20 min did not prevent this rise in protein excretion (3.9 +/- 2.4 and 5.8 +/- 2.6 mg/min/g at 30 to 40 and 55 to 65 min respectively, p less than 0.01, n = 4). Perfusion of aFx1A kidneys with C8-deficient (C8D) human plasma (25% v/v, n = 4) or C6D rabbit serum (25% v/v, n = 2) independently produced low levels of proteinuria comparable with BSA, but in combination, the two reagents restored enhanced protein excretion (n = 2). In aFx1A kidneys containing C5b-7, addition of C8 and C9 (C6D serum) after intervals of 20, 60, or 90 min immediately reconstituted heavy proteinuria. Thus, the magnitude of MAC-induced glomerular epithelial injury in rat MN is related to the complement dose. Altered glomerular permeability is delayed with respect to the onset of complement activation. Once sufficient C5b-9 is formed, proteinuria can develop despite cessation of new MAC assembly, implying that C5b-9 persists after formation. Moreover, the C5b-7 MAC intermediate is not eliminated rapidly in this model.
利用大鼠膜性肾病（MN）模型，我们研究了肾小球上皮细胞损伤的发展与补体膜攻击复合物（MAC）的形成及稳定性之间的关系。将分离的大鼠肾脏用缓冲牛血清白蛋白（BSA）或各种血浆（补体来源）进行灌注。用BSA灌注含有致肾炎量的针对肾小球上皮抗原的补体结合羊抗体（aFx1A）的肾脏（n = 5），以及用含50%（体积/体积）BSA的正常人血浆灌注正常肾脏（n = 6），在90分钟灌注期间蛋白质排泄量为0.30±0.02mg/分钟/克（对照组）。当以12.5%、25%和50%（体积/体积）的浓度将正常血浆添加到aFx1A肾脏的灌注液中时，蛋白质排泄呈时间和浓度依赖性增加。用25%血浆灌注导致0至20分钟出现基线蛋白尿，在20至40分钟时增加到2.8±0.9mg/分钟/克，在40至60分钟时增加到8.6±2.1mg/分钟/克（n = 4，与对照组相比p<0.01）。在20分钟时去除血浆并不能阻止蛋白质排泄的这种增加（在30至40分钟和55至65分钟时分别为3.9±2.4和5.8±2.6mg/分钟/克，p<0.01，n = 4）。用C8缺陷（C8D）人血浆（25%，体积/体积，n = 4）或C6缺陷兔血清（25%，体积/体积，n = 2）单独灌注aFx1A肾脏产生的蛋白尿水平较低，与BSA相当，但两者联合使用可恢复增强的蛋白质排泄（n = 2）。在含有C5b - 7的aFx1A肾脏中，在20、60或90分钟间隔后添加C8和C9（C6缺陷血清）可立即恢复重度蛋白尿。因此，在大鼠MN中MAC诱导的肾小球上皮损伤程度与补体剂量有关。肾小球通透性的改变相对于补体激活的开始有所延迟。一旦形成足够的C5b - 9，尽管新的MAC组装停止，蛋白尿仍可发展，这意味着C5b - 9在形成后持续存在。此外，在该模型中C5b - 7 MAC中间体不会迅速消除。
