IgA and IgG Immune Complexes Increase Human Macrophage C3 Biosynthesis
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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.
Geyer C, Chen H, Bye A, Manz X, Guerra D, Caniels T Life Sci Alliance. 2023; 6(11).
PMID: 37699657 PMC: 10497933. DOI: 10.26508/lsa.202302106.
Michelotti T, Kisby B, Flores L, Tegeler A, Fokar M, Crasto C Front Cell Dev Biol. 2022; 10:1025240.
PMID: 36313560 PMC: 9616121. DOI: 10.3389/fcell.2022.1025240.
Production of complement components by cells of the immune system.
Lubbers R, van Essen M, van Kooten C, Trouw L Clin Exp Immunol. 2017; 188(2):183-194.
PMID: 28249350 PMC: 5383442. DOI: 10.1111/cei.12952.
Immune complex glomerulonephritis following bone marrow transplantation in C3 deficient mice.
Welch T, Blystone L PLoS One. 2008; 3(10):e3334.
PMID: 18836527 PMC: 2553262. DOI: 10.1371/journal.pone.0003334.
Laufer J, Oren R, Goldberg I, Horwitz A, Kopolovic J, Chowers Y Clin Exp Immunol. 2000; 120(1):30-7.
PMID: 10759760 PMC: 1905612. DOI: 10.1046/j.1365-2249.2000.01168.x.