Expression of functionally active FcRn and the differentiated bidirectional transport of IgG in human placental endothelial cells
Abstract
The mechanism of selective transport of the immunoglobulins G from the placental stroma to the lumen of the fetal blood vessels has not been elucidated yet. It was postulated that the specific transport as well as the regulation of IgG level in the blood, involves the MHC class I related receptor FcRn for the Fc domain of IgG. We questioned whether human placental endothelial cells (HPEC) express FcRn and, if present, whether it is in a functionally active form. The experiments were performed on cultured HPEC and as positive control, human trophoblastic (JEG3) and mouse endothelial cells (SVEC) were used. Expression of FcRn, was demonstrated by indirect immunofluorescence and RT-PCR. The role of FcRn was assessed by quantifying the transcellular transport of [(125)I]-hIgG or [(125)I]-rF(ab')(2) fragments from the apical to basolateral surface, and in the reverse direction of HPEC grown on filters in a double chamber system. The intracellular pathway of FcRn or IgG was examined by electron microscopy using the proteins adsorbed to 5 nm and 20 nm colloidal gold particles, respectively. The results showed that: (a) FcRn is expressed by human placental endothelial cells, in a functionally active form; (b) transcytosis of IgG in HPEC is a time-dependent process that takes place preferentially from the basolateral to the apical compartment; and (c) both IgG and FcRn colocalize in an intracellular endocytic compartment, chloroquine sensitive. Together these data suggest that the reg…
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Some evidence points toward alternative Fc receptors in the further movement of IgG.
“some evidence, points toward alternative Fc receptors in the further movement of IgG (63, 64).”
From Factors Affecting the FcRn-Mediated Transplacental Transfer of Antibodies and Implications for Vaccination in Pregnancy (2017) · cites this paper as [63]
FcRn expression is dynamically regulated and broadly distributed throughout the uptake/endosomal pathway, although most evidence demonstrates that only a small fraction sits at the cell surface at any one point in time.
“our understanding is that FcRn expression is dynamically regulated and broadly distributed throughout the uptake/endosomal pathway, although most evidence demonstrates that only a small fraction sits at the cell surface at any one point in time [13–16].”
From The uptake, intracellular trafficking and recycling of FcRn-blocking therapeutics in human endothelial cells in vitro (2026) · cites this paper as [15]
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“FcRn expression in fetal endothelium, and some evidence, points toward alternative Fc receptors in the further movement of IgG (63, 64).”
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Sirina, J., D'Hooghe, L. E., Singhvi-Hanns, L. A., Cole, S. L., Shock, A., Holliday, N. D., & Stoddart, L. A. (2026) · Cellular Immunology · doi:10.1016/j.cellimm.2026.105128
- Authors
- Antohe, F., Rădulescu, L., Gafencu, A., Gheţie, V., & Simionescu, M.
- Affiliations
- Romanian Academy (RO)
- Venue
- Human Immunology
- Publisher
- Elsevier BV
- Published
- 2001-02
- Volume
- 62
- Issue
- 2
- Pages
- 93-105
- ISSN
- 0198-8859 (ISSN-L)
- OpenAlex
- W2002593667
- Cited by
- 175
- References
- 1
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 6 · 2020: 5 · 2019: 9 · 2018: 4 · 2017: 7 · 2016: 10 · 2015: 14 · 2014: 12 · 2013: 8 · 2012: 7
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Texas Southwestern Medical Center
- Academia Româna
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- neonatal Fc receptor, IgG transport, placental endothelial cells, transcytosis, bidirectional transport, endocytic compartments, placental barrier, trophoblast
- MeSH terms
- Animals, Biological Transport, Active, Cell Line, Transformed, Cells, Cultured, Endothelium, Vascular, Female, Humans, Immunoglobulin G, Immunity, Maternally-Acquired, Mice, Inbred C3H, Microscopy, Electron, Placenta, Pregnancy, Receptors, Fc, RNA, Messenger, Histocompatibility Antigens Class I, Fluorescent Antibody Technique, Indirect, Reverse Transcriptase Polymerase Chain Reaction, Mice
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