IgA and IgG immune complexes increase human macrophage C3 biosynthesis.
We have studied the effect of IgA- and IgG-containing immune complexes on the production of complement proteins C3, factor B and C2 by human monocyte-derived macrophages, using biosynthetic labelling, immunoprecipitation, sodium dodecyl sulphate-polyacrylamide gel (SDS-PAGE) and autoradiography. There was a consistent increase in C3 production and secretion with both IgA and IgG immune complexes. This increase appeared after a 24-hr incubation period of the macrophages in the presence of immune complexes. No change in the biosynthesis of factor B and C2 proteins was observed in these experiments. Concomitant with the enhanced C3 biosynthesis, the immune complexes caused an increase in macrophage tumour necrosis factor (TNF) production; 310 + 24 U/ml/5 x 10(5) cells and 430 + 51 U/ml/5 x 10(5) cells for IgA and IgG immune complexes, respectively, versus 12 + 8 U/ml/5 x 10(5) cells in the control cells. The presence of prednisolone (2 x 10(-5) M) or dexamethasone (1 x 10(-7) M) inhibited the immune complex-induced TNF production, but had no effect on C3-increased synthesis, suggesting that the effect of immune complexes was not mediated by endogenous TNF production. These findings may be relevant to the local inflammatory response in IgA immune complex-mediated diseases, including IgA nephropathy.
Laufer
J
J
Samuel Jared Kushnick Pediatric Immunology Laboratory, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Boichis
H
H
Farzam
N
N
Passwell
J H
JH
D000936:Antigen-Antibody Complex / Q000276:immunology*; D001345:Autoradiography; D003176:Complement C3 / Q000096:biosynthesis*; D004731:Endotoxins / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D003176:Complement C3; D004731:Endotoxins; D005938:Glucocorticoids; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha