Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Division of Obstetrics and Feto-Maternal Medicine, University Department of Obstetrics and Gynaecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Placenta. 2019 Mar;78:36-43. doi: 10.1016/j.placenta.2019.02.012. Epub 2019 Feb 28.
Starting from the second trimester of pregnancy, passive immunity is provided to the human fetus by transplacental transfer of maternal IgG. IgG transfer depends on the neonatal Fc receptor, FcRn. While FcRn localization in the placental syncytiotrophoblast (STB) has been demonstrated unequivocally, FcRn expression in placental-fetal endothelial cells (pFECs), which are part of the materno-fetal barrier, is still unclear. Therefore, this study aimed to elucidate the spatio-specific expression pattern of FcRn in placental tissue.
FcRn expression was investigated by western blotting in term placentas and in isolated human placental arterial and venous endothelial cells (HPAEC, HPVEC) using a validated affinity-purified polyclonal anti-peptide antibody against the cytoplasmic tail of FcRn α-chain. In situ localization of FcRn and IgG was studied by immunofluorescence microscopy on tissue sections of healthy term placentas.
FcRn expression was demonstrated in placental vasculature particularly, in HPAEC, and HPVEC. FcRn was localized in cytokeratin 7 STB and in CD31 pFECs in terminal as well as stem villi in situ. Additionally, CD68 placental macrophages exhibited FcRn expression in situ. Endogenous IgG partially co-localized with FcRn in STB, pFECs, and in placental macrophages.
Placental FcRn expression in endothelial cells and macrophages is analogous to the expression pattern in other organs. FcRn expression in pFECs suggests an involvement of FcRn in IgG transcytosis and/or participation in recycling/salvaging of maternal IgG present in the fetal circulation. FcRn expression in placental macrophages may account for recycling of monomeric IgG and/or processing and presentation of immune complexes.
自妊娠中期起，母体 IgG 通过胎盘转运会为人类胎儿提供被动免疫。IgG 的转移取决于新生儿 Fc 受体（FcRn）。虽然 FcRn 在胎盘合体滋养层（STB）中的定位已得到明确证实，但作为母胎屏障一部分的胎盘-胎儿内皮细胞（pFEC）中的 FcRn 表达仍不清楚。因此，本研究旨在阐明 FcRn 在胎盘组织中的空间特异性表达模式。
使用针对 FcRn α 链胞质尾的经验证的亲和纯化多克隆抗肽抗体，通过 Western blot 在足月胎盘和分离的人胎盘动脉和静脉内皮细胞（HPAEC、HPVEC）中研究 FcRn 的表达。通过免疫荧光显微镜在健康足月胎盘组织切片上研究 FcRn 和 IgG 的原位定位。
FcRn 在胎盘血管中表达，特别是在 HPAEC 和 HPVEC 中。FcRn 定位于 CK7 STB 和 CD31 pFEC 中，在终末和干绒毛中均有表达。此外，CD68 胎盘巨噬细胞在原位也表达 FcRn。内源性 IgG 部分与 STB、pFEC 和胎盘巨噬细胞中的 FcRn 共定位。
内皮细胞和巨噬细胞中的胎盘 FcRn 表达与其他器官的表达模式相似。pFEC 中的 FcRn 表达表明 FcRn 参与 IgG 的跨细胞转运和/或参与在胎儿循环中存在的母体 IgG 的再循环/回收。胎盘巨噬细胞中的 FcRn 表达可能解释了单体 IgG 的再循环和/或免疫复合物的加工和呈递。
