Salant D J, Adler S, Darby C, Capparell N J, Groggel G C, Feintzeig I D, Rennke H G, Dittmer J E
Kidney Int. 1985 Jun;27(6):938-50. doi: 10.1038/ki.1985.102.
To determine if the site of immune reaction could influence the mediation and morphological expression of glomerular injury in experimental anti-glomerular basement membrane (anti-GBM) nephritis and membranous nephropathy, we studied the events that followed the in situ reaction of rat antibody with antigen planted in either the GBM (especially the lamina rara interna) or in the subepithelial space (SE). Non-nephritogenic amounts of noncomplement-fixing sheep anti-GBM or anti-tubular brushborder antibody were injected into separate groups of rats to plant sheep IgG in the GBM and SE, respectively. Kidneys containing sheep IgG were then transplanted into naive recipients that were passively immunized with rat anti-sheep IgG. There was marked proteinuria after 2 days (antigen in GBM: 226 +/- 50.7; antigen in SE: 69 +/- 50.7 mg/24 hr) that was abrogated by prior depletion of complement in both groups (antigen in GBM: 10.2 +/- 1.7; antigen in SE: 14.3 +/- 8.7 mg/24 hr). When antigen was planted in SE, inflammatory-cell depletion with either anti-neutrophil (PMN) serum or lethal irradiation had no effect on proteinuria. In contrast, anti-PMN abolished proteinuria (12.0 +/- 5.6 mg/24 hr) and irradiation reduced it by 60% when antigen was in GBM. Glomeruli of kidneys with antigen in GBM were significantly larger and more hypercellular than those with antigen in SE after transplantation into immunized recipients. Endothelial cell injury and adherence of inflammatory cells to denuded GBM were prominent in the former (antigen in GBM), while glomeruli with antigen in SE showed only subepithelial deposits, adjacent slit-diaphragm displacement, and epithelial cell foot-process effacement. Thus, the reaction of antigen and antibody in glomeruli produced complement-mediated injury which was cell-independent when complex formation occurred on the outer aspect of the GBM but was cell-dependent when the same reagents reacted more proximally to the circulation. We therefore conclude that antigen distribution can critically influence the mediation and morphologic expression of immune glomerular injury and may, in part, account for variations in the clinical and histological manifestations of antibody-induced glomerular disease in humans.
为了确定免疫反应部位是否会影响实验性抗肾小球基底膜（anti-GBM）肾炎和膜性肾病中肾小球损伤的介导及形态学表现，我们研究了大鼠抗体与种植于肾小球基底膜（GBM，尤其是内疏松层）或上皮下间隙（SE）的抗原发生原位反应后的一系列事件。将非致肾炎量的非补体结合性羊抗GBM或抗肾小管刷状缘抗体分别注入不同组大鼠，以便将羊IgG分别种植于GBM和SE。然后将含有羊IgG的肾脏移植到用大鼠抗羊IgG被动免疫的未致敏受体中。两天后出现明显蛋白尿（GBM中有抗原：226±50.7；SE中有抗原：69±50.7mg/24小时），两组在预先消耗补体后蛋白尿均消失（GBM中有抗原：10.2±1.7；SE中有抗原：14.3±8.7mg/24小时）。当抗原种植于SE时，用抗中性粒细胞（PMN）血清进行炎症细胞清除或致死性照射对蛋白尿均无影响。相反，当抗原在GBM中时，抗PMN可消除蛋白尿（12.0±5.6mg/24小时），照射可使其减少60%。移植到免疫受体后，GBM中有抗原的肾脏的肾小球比SE中有抗原的肾脏的肾小球明显更大且细胞更多。在前者（GBM中有抗原）中，内皮细胞损伤以及炎症细胞黏附于裸露的GBM很突出，而SE中有抗原的肾小球仅表现为上皮下沉积物、相邻裂孔隔膜移位以及上皮细胞足突消失。因此，肾小球中抗原与抗体的反应产生了补体介导的损伤，当复合物形成于GBM外侧时该损伤不依赖细胞，但当相同试剂在更靠近循环的部位发生反应时则依赖细胞。我们因此得出结论，抗原分布可严重影响免疫性肾小球损伤的介导及形态学表现，并且可能部分解释了人类抗体诱导的肾小球疾病在临床和组织学表现上的差异。
