Intracellular processing of immune complexes formed on the surface of glomerular epithelial cells.

Abstract

Immune complexes formed on the surface of glomerular epithelial cells (GEC) resolve slowly and therefore result in inflammation of the glomerular capillary wall, as in the case of human membranous glomerulonephritis. The metabolic defect in the processing of these complexes has not been identified. Immune complexes of cationic bovine gamma-globulin (BGG) and anti-BGG were formed on cultured GEC, and their intracellular processing was followed by tracing the fate of radioiodinated and colloidal gold-labeled anti-BGG in the endosomal, lysosomal, and extracellular compartments. It was determined that the complexes were rapidly internalized in endosomes (50% saturation achieved in 10 min). The rate of expulsion of complexes was much slower (50% of internalized complex exteriorized in approximately 90 min). Of the internalized anti-BGG, < 5% were proteolytically degraded, suggesting an inefficient lysosomal processing. This aspect was studied further by separating anti-BGG colloidal gold-loaded vesicles by low-speed centrifugation and quantitating the lysosomal enzymes acid phosphatase and beta-galactosidase. At equilibrium approximately 10% of total cellular enzymes was associated with the vesicles. It was concluded that immune complexes are rapidly internalized by the GEC. However, lysosomal processing of the complexes is slow and inefficient. The majority of accumulated endosomes route back to the plasma membrane and discharge their contents in the medium in the form of free antibody.