Receptor-mediated endocytosis of immune complexes in rat liver sinusoidal endothelial cells is mediated by FcgammaRIIb2.
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 (FcgammaRs) 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 FcgammaRs in LSECs. Biochemical approaches and immunofluorescence microscopy were used to characterize the FcgammaR-mediated endocytosis of immune complexes (ICs). FcgammaRIIb2 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.


CONCLUSIONS
FcgammaRIIb2 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, FcgammaRIIb2 in rat LSECs is used as both a recycling receptor and a receptor for efficient IC clearance.
Department of Molecular Biosciences, University of Oslo, Norway.
Seyed Ali
SA
Mousavi
Marita
M
Sporstøl
Cathrine
C
Fladeby
Rune
R
Kjeken
Nicolas
N
Barois
Trond
T
Berg
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology; D007700:Kinetics; D008099:Liver / Q000276:immunology*; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D017452:Receptors, IgG / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D002966:Clathrin; C080571:Fc gamma receptor IIB; D017452:Receptors, IgG; D014443:Tyrosine