In vivo uptake of immune complexes by parenchymal and nonparenchymal liver cells in mice

Abstract

The binding and uptake of intravenously administered bovine serum albumin and horse ferritin by hepatocytes and nonparenchymal liver cells were studied in immune and nonimmune mice. As shown by fluorescence microscopy on isolated cells, bovine serum albumin was bound to the plasma membrane of hepatocytes from immune mice 20 min after injection (10 milligrams bovine serum albumin per animal). After 40 min the hepatocytes contained bovine serum albumin droplets in the cytoplasm. Hepatocytes with bovine serum albumin also showed membrane-bound or intracellular immunoglobulin G, but not third complement component. Hepatocytes from nonimmune mice did not show binding or uptake of bovine serum albumin or immunoglobulin G. Nonparenchymal liver cells from immune mice exhibited a strong granular pattern of mainly intracellular bovine serum albumin 20 and 40 min after administration. Nonparenchymal liver cells from nonimmune animals had a weak homogenous fluorescence under the same conditions. Using ferritin as the antigen, electron microscopy confirmed that hepatocytes from immune mice bind and take up foreign protein. The uptake of immune complexes by hepatocytes and nonparenchymal liver cells was quantified with iodinated antigens. Forty minutes after inoculation of 45 μg [125I]-bovine serum albumin, 106 hepatocytes from immune mice had in the mean (±SD) 3055 ± 564 cpm and 106 nonparenchymal liver cells had 43,177 ± 14,377 cpm. Cells from nonimmune mice had very low activity or were negative. Similar results were obtained with labeled ferritin as an antigen. In vitro-formed immune complexes with the same antigens and mouse antibodies were also taken up by hepatocytes and nonparenchymal liver cells after intravenous administration. In conclusion the hepatic clearance of immune complexes is a function of both hepatocytes and nonparenchymal cells.