Neonatal Fc Receptor Mediates Internalization of Fc in Transfected Human Endothelial Cells
- 1 December 2008
- journal article
- research article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 19 (12), 5490-5505
- https://doi.org/10.1091/mbc.e07-02-0101
Abstract
The neonatal Fc receptor, FcRn mediates an endocytic salvage pathway that prevents degradation of IgG, thus contributing to the homeostasis of circulating IgG. Based on the low affinity of IgG for FcRn at neutral pH, internalization of IgG by endothelial cells is generally believed to occur via fluid-phase endocytosis. To investigate the role of FcRn in IgG internalization, we used quantitative confocal microscopy to characterize internalization of fluorescent Fc molecules by HULEC-5A lung microvascular endothelia transfected with GFP fusion proteins of human or mouse FcRn. In these studies, cells transfected with FcRn accumulated significantly more intracellular Fc than untransfected cells. Internalization of FcRn-binding forms of Fc was proportional to FcRn expression level, was enriched relative to dextran internalization in proportion to FcRn expression level, and was blocked by incubation with excess unlabeled Fc. Because we were unable to detect either surface expression of FcRn or surface binding of Fc, these results suggest that FcRn-dependent internalization of Fc may occur through sequestration of Fc by FcRn in early endosomes. These studies indicate that FcRn-dependent internalization of IgG may be important not only in cells taking up IgG from an extracellular acidic space, but also in endothelial cells participating in homeostatic regulation of circulating IgG levels.Keywords
This publication has 60 references indexed in Scilit:
- FcRn: an IgG receptor on phagocytes with a novel role in phagocytosisBlood, 2006
- Humanized IgG1 Variants with Differential Binding Properties to the Neonatal Fc Receptor: Relationship to Pharmacokinetics in Mice and PrimatesDrug Metabolism and Disposition, 2006
- Analysis of a family of antibodies with different half-lives in mice fails to find a correlation between affinity for FcRn and serum half-lifeMolecular Immunology, 2006
- From Sorting Endosomes to Exocytosis: Association of Rab4 and Rab11 GTPases with the Fc Receptor, FcRn, during RecyclingMolecular Biology of the Cell, 2005
- Characterization of the porcine neonatal Fc receptor—potential use for trans‐epithelial protein deliveryImmunology, 2005
- A passionate kiss, then run: exocytosis and recycling of IgG by FcRnTrends in Cell Biology, 2005
- Human Neonatal Fc Receptor Mediates Transport of IgG into Luminal Secretions for Delivery of Antigens to Mucosal Dendritic CellsImmunity, 2004
- The End2 mutation in CHO cells slows the exit of transferrin receptors from the recycling compartment but bulk membrane recycling is unaffectedThe Journal of cell biology, 1993
- Segregation of transferrin to a mildly acidic (pH 6.5) para-golgi compartment in the recycling pathwayCell, 1984
- Exocytosis of pinocytosed fluid in cultured cells: kinetic evidence for rapid turnover and compartmentation.The Journal of cell biology, 1981