Transcellular transport and membrane insertion of the C5b-9 membrane attack complex of complement by glomerular epithelial cells in experimental membranous nephropathy.
Transcellular transport and membrane insertion of the C5b-9 membrane attack complex of complement by glomerular epithelial cells in experimental membranous nephropathy.
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DOI：
10.4049/jimmunol.143.2.546
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发表时间：
1989-07
影响因子：
4.4
通讯作者：
D. Kerjaschki;M. Schulze;S. Binder;Renate Kain;P. Ojha;M. Susani;Reinhard Horvat;P. Baker;W. Couser
中科院分区：
文献类型：
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作者：
D. Kerjaschki;M. Schulze;S. Binder;Renate Kain;P. Ojha;M. Susani;Reinhard Horvat;P. Baker;W. Couser
C5b-9复合体在实验性膜性肾病(MN)大鼠肾小球中的沉积在蛋白尿的发生发展中起重要作用。本研究用抗C5b-9(M)新抗原的单抗对被动型Heymann肾炎(PHN)中的C5b-9进行了定位。并与大鼠连续注射阳离子人免疫球蛋白和兔抗人免疫球蛋白所致的MN模型进行了比较。在PHN中，C5b-9存在于：1)免疫沉淀物(ID)和靠近ID的足突细胞膜上；2)靠近ID的肾小球上皮细胞(GEC)的网状蛋白包裹的小凹和细胞质中的膜泡，与绵羊的Ig G和gp330 Ag分离；3)在GEC的多囊泡体中高浓度表达；4)与尿腔中的膜泡有关，可能是膜泡小体的胞外内容物。相反，在阳离子Ig G-MN模型中，C5b-9主要分布在ID中，而在GEC中很少。通过冷冻断裂电子显微镜，我们进一步发现PHN中的200-250-A膜内颗粒存在于足突“底”的细胞膜中，类似于插入膜的人类C5b-9(M)。免疫印迹法进一步检测C5b-9的降解产物，免疫印迹法检测10万克PHN大鼠尿液。这些结果表明，在PHN中，C5b-9被插入到GEC的细胞膜中，并通过一种明显保护细胞免受插入膜的C5b-9积聚的细胞机制选择性地内吞和跨GEC转运。
Deposition of the C5b-9 complex of C in glomeruli of rats with experimental membranous nephropathy (MN) is essential for the development of proteinuria. In this investigation C5b-9 was localized in the passive Heymann nephritis (PHN) by immunoelectron microscopy with a mAb specific for C5b-9(m) neoantigen. Its distribution was compared with that in another model of MN induced by successive injections of cationic human IgG and rabbit anti-human IgG into rats. In PHN C5b-9 was found: 1) in the immune deposits (ID), and on the cell membranes of foot processes close to the ID; 2) in clathrin-coated pits of the glomerular epithelial cells (GEC) close to the ID and in membrane vesicles in the cytoplasm, separated from sheep IgG and the gp330 Ag; 3) in high concentration in multivesicular bodies of GEC; and 4) in association with membrane vesicles in the urinary space which presumably are the exocytosed content of membrane vesicular bodies. By contrast, in the cationic IgG-MN model C5b-9 was found mostly in ID, but rarely within the GEC. By freeze-fracture electron microscopy we have further identified 200- to 250-A intramembrane particles in PHN in the cell membranes of the "soles" of the foot processes which resemble membrane inserted human C5b-9(m). Degradation products of C5b-9 were further detected by immunoblotting of a 100,000 x g pellet of PHN rat urine. These results indicate that, in PHN, C5b-9 is inserted into the cell membranes of GEC, and that it is selectively endocytosed and transported across GEC by a cellular mechanism which apparently protects the cell from accumulation of membrane-inserted C5b-9.