Transcellular transport and membrane insertion of the C5b-9 membrane attack complex of complement by glomerular epithelial cells in experimental membranous nephropathy.
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.
Kerjaschki
D
D
Institute of Pathological Anatomy, University of Vienna, Austria.
Schulze
M
M
Binder
S
S
Kain
R
R
Ojha
P P
PP
Susani
M
M
Horvat
R
R
Baker
P J
PJ
Couser
W G
WG
D000818:Animals; D000936:Antigen-Antibody Complex / Q000032:analysis; D001692:Biological Transport; D002462:Cell Membrane / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000502:physiology* / Q000652:urine; D004705:Endocytosis; D004848:Epithelium / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D005110:Extracellular Space / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000276:immunology* / Q000473:pathology / Q000652:urine; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains
D000936:Antigen-Antibody Complex; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins