Divalency of the monoclonal antibody 5-1-6 is required for induction of proteinuria in rats.
A single i.v. injection of 3 mg of the F(ab')2 fragment of MoAb 5-1-6 into rats induced immediate proteinuria (128.1 +/- 80.7 mg/24 h on day 1) which lasted 1-2 days. In contrast, rats administered 10 mg of the corresponding Fab fragment did not develop abnormal proteinuria even though an equivalent dose of the intact MoAb 5-1-6 far exceeded the nephritogenic dose. The total kidney binding of 125I-Fab fragment was 209.5 +/- 34.3 micrograms/2 kidneys. This exceeded that obtained by injection of 3 mg MoAb 5-1-6 IgG1 (58.9 +/- 12.5 micrograms/2 kidneys at 1 h) and was similar to that obtained following injection of 3 mg F(ab')2 fragment (235.3 +/- 16.9 micrograms/2 kidneys). Immunofluorescence (IF) showed a linear pattern along the glomerular capillary wall at 1 h after the administration of MoAb 5-1-6 IgG1, F(ab')2 or Fab fragment. On day 5, fine to coarse granules were observed scattered in F(ab')2-injected rat glomeruli, whereas granules were densely localized in Fab-injected rat glomeruli. Complement-depleted rats injected with 3 mg of MoAb 5-1-6 IgG1 developed proteinuria with the same time course as non-depleted rats. This observation, together with the ability of F(ab')2 to induce proteinuria, indicates that proteinuria induced by MoAb 5-1-6 is complement-independent. This study suggests that MoAb 5-1-6-induced proteinuria is initiated by cross-linking of the epitopes by divalent MoAb 5-1-6 and is independent of complement activity.
Department of Immunology, Niigata University School of Medicine, Japan.
M
M
Narisawa
H
H
Kawachi
T
T
Oite
F
F
Shimizu
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011507:Proteinuria / Q000276:immunology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D003165:Complement System Proteins