Transcellular transport and membrane insertion of the C5b-9 membrane attack complex of complement by glomerular epithelial cells in experimental membranous nephropathy.

作者：Dontscho Kerjaschki, M Schulze, Susanne Binder, Renate Kain, P P Ojha, Martin Susani, Reinhard Horvat, Patricia J. Baker, William G. Couser · 发表于：The Journal of Immunology · 年份：1989 · DOI：10.4049/jimmunol.143.2.546 · 被引用次数：135 · 研究领域：Renal Diseases and Glomerulopathies、Complement system in diseases、Reproductive System and Pregnancy

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 endocyto...