Expression of functionally active FcRn and the differentiated bidirectional transport of IgG in human placental endothelial cells

Antohe, Felicia; Rădulescu, Luminiţa; Gafencu, Anca Violeta; Gheţie, Victor; Simionescu, Maya

doi:10.1016/s0198-8859(00)00244-5

Cited by 161 publications

(125 citation statements)

References 34 publications

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“…FcRn expression in endothelial cells is primarily in intracellular organelles, with limited cell surface expression (5,9). For nearly all FcRn species and IgG isotypes analyzed to date, the FcRn-IgG interaction is highly pH dependent, with binding occurring at pH 6.0 that becomes progressively weaker as neutral pH is approached (10 -13).…”

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confidence: 99%

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Visualizing the Site and Dynamics of IgG Salvage by the MHC Class I-Related Receptor, FcRn

Ober¹,

Martinez

Vaccaro

et al. 2004

The Journal of Immunology

271

309

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The MHC class I-related receptor, FcRn, plays a central role in regulating the serum levels of IgG. FcRn is expressed in endothelial cells, suggesting that these cells may be involved in maintaining IgG levels. We have used live cell imaging of FcRn-green fluorescent protein transfected human endothelial cells to analyze the intracellular events that control IgG homeostasis. We show that segregation of FcRn-IgG complexes from unbound IgG occurs in the sorting endosome. FcRn or FcRn-IgG complexes are gradually depleted from sorting endosomes to ultimately generate multivesicular bodies whose contents are destined for lysosomal degradation. In addition, the pathways taken by FcRn and the transferrin receptor overlap, despite distinct mechanisms of ligand uptake. The studies provide a dynamic view of the trafficking of FcRn and its ligand and have relevance to understanding how FcRn functions to maintain IgG homeostasis.

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confidence: 99%

“…For several reasons, IgG uptake is believed to be via fluid phase pinocytosis rather than receptor mediated. First, limited, if any, surface FcRn expression can be detected (5,9). Second, even if cell surface expression of FcRn occurs, the extracellular pH is generally not permissive for FcRn binding to IgG (10 -13).…”

mentioning

confidence: 99%

Visualizing the Site and Dynamics of IgG Salvage by the MHC Class I-Related Receptor, FcRn

Ober¹,

Martinez

Vaccaro

et al. 2004

The Journal of Immunology

271

309

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“…The receptor known as neonatal FcR (FcRn) was subsequently cloned and was found to be responsible for the protection of IgG from intracellular metabolism (13,14). FcRn is composed of two subunits: an H chain (a MHC class I-like molecule); and an L chain, ␤ 2 -microglobulin (␤ 2 m) (13) and is expressed in many tissues including blood vessels, lung, liver, intestine, and kidney (15)(16)(17). The current understanding of FcRn function is as follows: IgG is taken up by endothelial cells that line the vasculature by fluid phase pinocytosis, followed by pH-dependent binding to FcRn (18,19) in acidic endosomes, thereby protecting IgG from releasing into lysosomal endosomes where protein degradation occurs.…”

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confidence: 99%

Amelioration of Experimental Autoimmune Myasthenia Gravis in Rats by Neonatal FcR Blockade

García

Santoro

et al. 2007

The Journal of Immunology

106

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The neonatal FcR (FcRn) plays a critical role in IgG homeostasis by protecting it from a lysosomal degradation pathway. It has been shown that IgG has an abnormally short half-life in FcRn-deficient mice and that FcRn blockade significantly increases the catabolism of serum IgG in mice. Therefore, reduction of serum IgG half-life may have therapeutic benefits in Ab-mediated autoimmune diseases. We have studied the therapeutic effects of an anti-rat FcRn mAb, 1G3, in two rat models of myasthenia gravis, a prototypical Ab-mediated autoimmune disease. Passive experimental autoimmune myasthenia gravis was induced by administration of an anti-acetylcholine receptor (AChR) mAb, and it was shown that treatment with 1G3 resulted in dose-dependent amelioration of the disease symptoms. In addition, the concentration of pathogenic Ab in the serum was reduced significantly. The effect of 1G3 was also studied in an active model of experimental autoimmune myasthenia gravis in which rats were immunized with AChR. Treatment with 1G3 significantly reduced the severity of the disease symptoms as well as the levels of total IgG and anti-AChR IgG relative to untreated animals. These data suggest that FcRn blockade may be an effective way to treat Ab-mediated autoimmune diseases.

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“…This receptor, composed by an alpha chain (FCGRT) in association with Beta-2-Microglobulin (B2M), is expressed in different cell types of various organs and systems, in a wide variety of animal species, but endothelial cells are considered the main mediators of FcRn-IgG processes (Johnson et al, 1975;Rodewald, 1980;Ghetie et al, 1996;Borvak et al, 1998;Cianga et al, 2011;Rath et al, 2013). It has been demonstrated in endothelial cells of the lung, term placenta villi and retino-choroids (Borvak et al, 1998;Antohe et al, 2001;Ward et al, 2003;Radulescu et al, 2004;Perez-Montoyo et al, 2009;Powner et al, 2014). The FcRn thus seems widely distributed in the human body.…”

Section: Introductionmentioning

confidence: 99%

Potential of HMEC-1 Line and HUVEC Primary Culture Cells to Study the Neonatal IgG Fc Receptor <i>in vitro</i>

Ortiz-Alegría

Cañedo-Solares

Vadillo-Ortega

et al. 2016

American Journal of Immunology

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The neonatal IgG Fc receptor (FcRn) plays an important role in IgG homeostasis and immunity passive transfer. Fine points regarding these mechanisms, however, are still emerging. In order to obtain information about these phenomena, it is essential to have in vitro models of endothelium that express this receptor. In this study we chose two widely used models of human endothelial cells: the semi-immortalized and stable cell line HMEC-1 (CDC/USA) and the Human Umbilical Vein Endothelial Cells (HUVECs) which maintain morphological, phenotypical and functional characteristics of human micro and macro-vasculature endothelia, respectively. We found that both cells express the FcRn mRNA and protein using real-time RT-PCR, flow cytometry and confocal microscopy, respectively. We detected differences in mRNA expression levels in HUVECs among individuals. The protein was found on the cell surface but also intracellularly within vesicles. This study supports the use of two cell types as models of FcRn expression, allowing either to understand or to manipulate the mechanisms in which the receptor is involved in vivo.

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Expression of functionally active FcRn and the differentiated bidirectional transport of IgG in human placental endothelial cells

Cited by 161 publications

References 34 publications

Visualizing the Site and Dynamics of IgG Salvage by the MHC Class I-Related Receptor, FcRn

Visualizing the Site and Dynamics of IgG Salvage by the MHC Class I-Related Receptor, FcRn

Amelioration of Experimental Autoimmune Myasthenia Gravis in Rats by Neonatal FcR Blockade

Potential of HMEC-1 Line and HUVEC Primary Culture Cells to Study the Neonatal IgG Fc Receptor <i>in vitro</i>

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