Fc gamma receptor IIb participates in maternal IgG trafficking of human placental endothelial cells.

Fc gamma receptor IIb participates in maternal IgG trafficking of human placental endothelial cells.
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DOI:
10.3892/ijmm.2015.2141
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发表时间:
2015-05
影响因子:
5.4
通讯作者:
Takizawa T
Takizawa T
中科院分区:
医学3区
文献类型:
--
作者:
Ishikawa T;Takizawa T;Iwaki J;Mishima T;Ui-Tei K;Takeshita T;Matsubara S;Takizawa T

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人胎盘转移母体免疫球蛋白对胎儿和新生儿的免疫起着至关重要的作用。低亲和力免疫球蛋白γFc区受体IIb2(FCGR2B2或FcγRIIb2)仅在人胎盘内皮细胞内含免疫球蛋白的囊泡状细胞器(FCGR2B2室)中表达,因此我们推测FCGR2B2室具有免疫球蛋白转运体的功能。在这项研究中,为了验证这一假说,我们使用携带增强型GFP标记的FCGR2B2(pFCGR2B2-EGFP)的质粒载体转染的人脐静脉内皮细胞,对FCGR2B2隔室内的IgG转运进行了体外生物成像分析。FCGR2B2-EGFP信号在体内检测到类似于FCGR2B2隔室的细胞内泡状结构。PFCGR2B2-EGFP转染组的免疫球蛋白内化和转胞作用显著高于模型转染组,且大部分内化的免疫球蛋白与FCGR2B2-EGFP信号共定位。此外,我们从人胎盘中分离出FCGR2B2区段,发现Rab蛋白家族[RAS相关蛋白Rab家族(RABS)]与FCGR2B2区段相关。在RAB中,RAB3D主要在胎盘内皮细胞表达。小干扰RNA(SiRNA)下调RAB3D后,细胞外周FCGR2B2-EGFP信号明显减少。综上所述,这些发现表明,FCGR2B2隔室参与了母体免疫球蛋白跨人胎盘内皮细胞的跨细胞转运,RAB3D在调节FCGR2B2隔室的细胞内动力学方面发挥了作用。
The human placental transfer of maternal IgG is crucial for fetal and newborn immunity. Low-affinity immunoglobulin gamma Fc region receptor IIb2 (FCGR2B2 or FcγRIIb2) is exclusively expressed in an IgG-containing, vesicle-like organelle (the FCGR2B2 compartment) in human placental endothelial cells; thus, we hypothesized that the FCGR2B2 compartment functions as an IgG transporter. In this study, to examine this hypothesis, we performed in vitro bio-imaging analysis of IgG trafficking by FCGR2B2 compartments using human umbilical vein endothelial cells transfected with a plasmid vector containing enhanced GFP-tagged FCGR2B2 (pFCGR2B2-EGFP). FCGR2B2-EGFP signals were detected as intracellular vesicular structures similar to FCGR2B2 compartments in vivo. The internalization and transcytosis of IgG was significantly higher in the pFCGR2B2-EGFP-transfected cells than in the mock-transfected cells, and the majority of the internalized IgG was co-localized with the FCGR2B2-EGFP signals. Furthermore, we isolated FCGR2B2 compartments from the human placenta and found that the Rab family of proteins [RAS-related protein Rab family (RABs)] were associated with FCGR2B2 compartments. Among the RABs, RAB3D was expressed predominantly in placental endothelial cells. The downregulation of RAB3D by small interfering RNA (siRNA) resulted in a marked reduction in the FCGR2B2-EGFP signals at the cell periphery. Taken together, these findings suggest that FCGR2B2 compartments participate in the transcytosis of maternal IgG across the human placental endothelium and that RAB3D plays a role in regulating the intracellular dynamics of FCGR2B2 compartments.
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