| Project/Area Number |
16390479
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
TAKIZAWA Toshihiro Nippon Medical School, Graduate School of Medicine, Professor (90271220)
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| Co-Investigator(Kenkyū-buntansha) |
TOSHIYUKI Takeshita Nippon Medical School, Graduate School of Medicine, Professor (60188175)
GOTO Tadashi Nippon Medical School, Faculty of Medicine, Associate Professor (50049855)
ISHIKAWA Tomoko Nippon Medical School, Faculty of Medicine, Research Associate (70212850)
MORI Miki Nippon Medical School, Faculty of Medicine, Research Associate (00277576)
ISHIKAWA Gen Nippon Medical School, Faculty of Medicine, Research Associate (20287767)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2004: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | human placenta / IgG / endothelial cells / Fc gamma receptor IIb / intracellular trafficking / Proteomics / immunohistochemistry / Fc受容体 / カベオラ / 免疫細胞化学 |
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| Research Abstract |
Human placental transfer of IgG from maternal circulation to that of the fetus is crucial for fetal and newborn immunity. This process requires that IgG broach two cellular layers of the placenta. IgG transport across the first layer, the syncytiotrophoblast, is mediated by the MHC-related Fc receptor for IgG, FcRn. The second layer, the villus endothelium, was until recently thought to allow IgG movement nonspecifically by constitutive transcytosis in caveolae. Recently, it has been shown that the villus endothelium expresses a separate Fc receptor for IgG, the inhibitory motif-bearing FcγRIIb seen on macrophages and B cells. We characterized the FcγRIIb-containing compartment in human fetal endothelial cells by ultrahigh-resolution immunofluorescence and immunoelectron microcopies. About half of these FcγRIIb organelles contain IgG; the remainder lack IgG. The majority fraction (~80%) of IgG containing organelles is associated with FcγRIIb. No IgG-containing organelles are associated
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with caveolin. These findings are compatible with FcγRIIb-mediated transfer of IgG across the fetal endothelial cells, independently of caveolae. Next, we verified the expression of FcγRIIb in the placental endothelial cells and use reverse transcriptase-polymerase chain reaction and sequencing analyses to define the expressed FCGR2B mRNA transcript variant. The mRNA sequence of FCGR2B expressed specifically in the endothelial cells is that of transcript variant 2. In addition, proteomics and microarray analyses of the villus endothelium discovered candidate proteins that were probably associated with FcγRIIb-vesicles. Further functional characterization of these proteins in the IgG-transcytosis pathway remains to be elucidated. In addition, a proteomics screen of human placental microvillous syncytiotrophoblast revealed the expression of dysferlin, a plasma membrane repair protein related with certain muscular dystrophies. We found a novel FcγRIIb-defined, IgG-containing organelle in the villus endothelium, unassociated with caveolae. This organelle is likely a key structure for the transcytosis of IgG in the human placenta. Less
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