Receptor-mediated endocytosis of immune complexes in rat liver sinusoidal endothelial cells is mediated by FcγRIIb2

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Abstract
Liver sinusoidal endothelial cells (LSECs) display a number of receptors for efficient uptake of potentially injurious molecules. The receptors for the Fc portion of immunoglobulin G (IgG) antibodies (FcγRs) regulate a number of physiological and pathophysiological events. We used reverse transcription polymerase chain reaction (RT-PCR) and Western blotting to determine the expression of different types of FcγRs in LSECs. Biochemical approaches and immunoflorescence microscopy were used to characterize the FcγR-mediated endocytosis of immune complexes (ICs). FcγRIIb2 was identified as the main receptor for the efficient uptake of ICs in LSECs. The receptor was shown to use the clathrin pathway for IC uptake; however, the association with lipid rafts may slow the rate of its internalization. Moreover, despite trafficking through lysosomal integral membrane protein-II (LIMP-II)–containing compartments, the receptor was not degraded. Finally, it was shown that the receptor recycles to the cell surface both with and without IC. Conclusion: FcγRIIb2 is the main receptor for endocytosis of ICs in rat LSECs. Internalized ICs are degraded with slow kinetics, and IC internalization is not linked to receptor downregulation. After internalization, the receptor recycles to the cell surface both with and without ICs. Thus, FcγRIIb2 in rat LSECs is used as both a recycling receptor and a receptor for efficient IC clearance. (Hepatology 2007.)