Mousavi Seyed Ali, Sporstøl Marita, Fladeby Cathrine, Kjeken Rune, Barois Nicolas, Berg Trond
Department of Molecular Biosciences, University of Oslo, Norway.
Hepatology. 2007 Sep;46(3):871-84. doi: 10.1002/hep.21748.
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.
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.
肝窦内皮细胞（LSECs）具有多种受体，可有效摄取潜在有害分子。免疫球蛋白G（IgG）抗体Fc段的受体（FcγRs）调节许多生理和病理生理事件。我们使用逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法来确定LSECs中不同类型FcγRs的表达。采用生化方法和免疫荧光显微镜对FcγR介导的免疫复合物（ICs）内吞作用进行表征。FcγRIIb2被确定为LSECs中有效摄取ICs的主要受体。该受体通过网格蛋白途径摄取ICs；然而，与脂筏的结合可能会减慢其内化速率。此外，尽管通过含有溶酶体整合膜蛋白-II（LIMP-II）的区室运输，但该受体并未降解。最后，结果表明该受体在有或没有IC的情况下均可循环至细胞表面。
FcγRIIb2是大鼠LSECs中ICs内吞作用的主要受体。内化的ICs以缓慢的动力学降解，IC内化与受体下调无关。内化后，该受体在有或没有ICs的情况下均可循环至细胞表面。因此，大鼠LSECs中的FcγRIIb2既作为循环受体，又作为有效清除ICs的受体。
