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, immunopre cipitation, sodium dodecyl sulphate-polyacrylamide gel(SDS-PAGE) and a utoradiography. There was a consistent increase in C3 production and s ecretion with both IgA and IgG immune complexes. This increase appeare d after a 24-hr incubation period of the macrophages in the presence o f immune complexes. No change in the biosynthesis of factor B and C2 p roteins was observed in these experiments. Concomitant with the enhanc ed C3 biosynthesis, the immune complexes caused an increase in macroph age tumour necrosis factor (TNF) production; 310 + 24 U/ml/5 x 10(5) c ells and 430 + 51 U/ml/5 x 10(5) cells for IgA and IgG immune complexe s, respectively, versus 12 + 8 U/ml/5 x 10(5) cells in the control cel ls. 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 im mune complexes was not mediated by endogenous TNF production. These fi ndings may be relevant to the local inflammatory response in IgA immun e complex-mediated diseases, including IgA nephropathy.