Hepatic uptake of autologous immune complexes in the rat.

The hepatic uptake of autologous immune complexes (ICx) was studied in Wistar rats immunized with bovine serum albumin (BSA). After attaining a suitable serum titre of rat anti-BSA Ig (RatABSA) they were injected intravenously with 2 mg BSA. The antibody levels were measured with an ELISA and the rate of disappearance of BSA from the circulation was studied by labelling the antigen with FITC. At various times after injection of BSA the uptake of ICx in the different types of liver cells was studied with the immunoperoxidase technique at the light microscope and ultrastructural levels. Within 5 min of injection with BSA ICx appeared to be bound and internalized by Kupffer cells, endothelial cells, and hepatocytes. After 2 h hepatocytes showed many large vacuoles containing ICx, whereas most microvilli had disappeared from the sinusoidal plasma membrane of these cells. In rats with a high antibody titre BSA had disappeared almost completely (92%) from the blood within 2 h. Rats with low antibody titre showed a lower disappearance rate of BSA, whereas a considerable amount of antibody was still present in the blood after 2 h. We conclude that autologous ICx are bound and endocytosed by Kupffer cells, endothelial cells and hepatocytes of the liver. The affinity for the antigen from the circulation. Uptake of autologous ICx by hepatocytes occurs only in the presence of large amounts of circulating ICx.

Immunohistochemical demonstration of FC receptors in rat tissues using immune complexes as ligand.

To demonstrate the presence and localization of Fc receptors, rat liver cryostat sections were incubated with heterologous and autologous immune complexes (ICx) and immunoglobulin (Ig) aggregates. Binding was demonstrated using the immunoperoxidase technique. Autologous and heterologous ICx as well as aggregates from human and rat Ig appeared to bind to the sinusoidal wall. ICx bind in preference to aggregates. Monomeric Ig and aggregated Ig from swine and rabbit did not bind. The results demonstrated that ICx and rat and human Ig aggregates were bound via an Fc receptor. This Fc receptor was still intact in livers from carbontetra chloride and galactosamine treated rats. The receptor could also be demonstrated on spleen macrophages and on kidney interstitial cells. This method turned out to be an useful functional histochemical method to localize Fc receptors and to demonstrate their affinity and species specificity in tissues.

Studies on the mechanism of binding and uptake of immune complexes by various cell types of rat liver in vivo.

Soluble heterologous immune complexes (IC) were used to study the mechanism of IC binding to rat liver in vivo. Binding of IC to the various cell types of the liver, endothelial cells, hepatocytes, and Kupffer cells, was only inhibited by aggregated swine immunoglobulins. Binding was not inhibited by the absence of complement components. Intravenous injection of asialoglycoproteins, to block the galactose receptor, could not prevent IC binding. We conclude that Fc receptors play an important role in the binding of soluble heterologous IC to hepatocytes, endothelial cells, and Kupffer cells.

A histochemical study about the involvement of rat liver cells in the uptake of heterologous immune complexes from the circulation.

Intravenously injected immune complexes (ICx) composed of bovine serum albumin (BSA) and rabbit anti-BSA were taken up by the liver. Insoluble complexes, made in antibody excess, were rapidly taken up by Kupffer cells and were metabolized within 24 h. Soluble complexes, made in antigen excess, were only partly taken up by Kupffer cells. In addition these complexes were bound, taken up and metabolized by endothelial cells. Until 2 h after injection soluble complexes could also be observed along the microvilli of hepatocytes. No signs of endocytosis in hepatocytes could be observed. It is concluded, that ICx can be taken up by Kupffer cells as well as by endothelial cells. The physical state of the complexes, soluble or insoluble, determines the cell type in which uptake occurs.