IgG Immune Complex Binding to and Activation of Liver Cells

Abstract

Background/Aims: The aim was to study IgG immune complex (IC) binding to isolated hepatocytes, Kupffer cells (KCs) and sinusoidal endothelial cells (SECs). Further, we wished to analyze the capacity of IgG ICs to induce release of reactive oxygen metabolites by the IC-binding liver cells. Methods: ICs were formed between ¹²⁵I-tyramine-cellobiose-labelled dinitrophenyl-conjugated human serum albumin (¹²⁵I-TC-DNP₁₀HSA) and polyclonal rabbit IgG antibodies. Binding of ICs to different rat liver cells in suspension was studied at 4°C. Production of reactive oxygen metabolites was measured by luminol-enhanced chemiluminescence at 37°C. Results: IgG mediated binding of ¹²⁵I-TC-DNP₁₀HSA to both KCs and SECs, but not to hepatocytes. The binding showed saturation kinetics and was blocked by an excess of unlabelled IgG-ICs. IgG-ICs activated KCs, but not SECs, to a chemiluminescence response. Conclusions: Both KCs and SECs bind IgG-ICs in vitro, probably via Fc receptor interaction. IgG-ICs activate KCs to produce reactive oxygen metabolites. The binding of IgG-ICs to isolated hepatocytes is small.

Infliximab Exerts No Direct Hepatotoxic Effect on HepG2 Cells In Vitro

“…After forming an immune complex with TNF-α, this complex is cleared by the mononuclear phagocytic system in the liver via Fc receptor-mediated interactions that in turn can activate Kupffer cells. These resident macrophages of the liver located in hepatic sinusoids do release reactive oxygen species which may lead to local damage of hepatocytes [11–13]. During infliximab therapy, increased formation of anti-nuclear antibodies has been observed [14], most possibly due to the fact that binding of infliximab to transmembrane TNF on the cell surface induces apoptosis, leading to the release of nucleosomes and the generation of anti-nuclear antibodies [15].…”

Cholestatic Liver Disease after Rituximab and Adalimumab and the Possible Role of Cross-Reacting Antibodies to Fab 2 Fragments

“…The formation of circulating immune complexes (IC) has to be considered. Circulating IgG-ICs are normally efficiently eliminated by the reticuloendothelial system of the liver [22] . Whether or not hepatocytes or cholangiocytes are involved in the uptake of IgG-ICs is controversial, although the prevailing opinion is that they are not.…”

“…Whether or not hepatocytes or cholangiocytes are involved in the uptake of IgG-ICs is controversial, although the prevailing opinion is that they are not. Kupffer cells are beyond doubt involved in the process, but also the sinusoidal cells can take part in the uptake of Ig-ICs via Fc receptor interaction [22] , [23] . The next unsolved problem implicates the question, whether the antibodies against Fab fragment in general abrogate the pharmacodynamic effect of rituximab and adalimumab.…”