Ellinger I, Rothe A, Grill M, Fuchs R
Department of Pathophysiology, University of Vienna, Währinger Gürtel 18-20, Vienna, A-1090, Austria.
Exp Cell Res. 2001 Oct 1;269(2):322-31. doi: 10.1006/excr.2001.5330.
The murine neonatal Fc receptor, FcRn, carries out two functions: materno-fetal IgG delivery and maintenance of serum IgG homeostasis. During human pregnancy maternal IgG is transferred across placental syncytiotrophoblasts presumably by the human homolog of FcRn, hFcRn. Trophoblast-derived BeWo cells express hFcRn endogenously and can be considered as a model system to investigate IgG transport in syncytiotrophoblasts. Using a pulse-chase protocol, we here demonstrate that polarized BeWo cells exhibit not only apical to basolateral transcytosis but also apical IgG recycling. Thus, for the first time we demonstrate that epithelial cells can be involved in both materno-fetal IgG transmission and regulation of serum IgG levels. Lowering the temperature from 37 to 16 degrees C reduced, but did not block, IgG recycling and transcytosis. Microtubule-disruption by nocodazole did not influence transcytosis or apical recycling. Disassembly of filamentous actin by cytochalasin D stimulated apical endocytosis and recycling, while transcytosis remained unaffected. In summary, in BeWo cells apically internalized IgG enters both a transcytotic and recycling pathway. While the transcytotic route is temperature-sensitive but independent from microtubules and actin filaments, the apical recycling pathway is temperature-influenced and stimulated by actin disassembly, suggestive for the involvement of distinct endosome subcompartments in transcytosis and recycling.
小鼠新生儿Fc受体FcRn具有两种功能：母胎IgG传递和维持血清IgG稳态。在人类妊娠期间，母体IgG大概通过FcRn的人类同源物hFcRn穿过胎盘合体滋养层细胞。滋养层来源的BeWo细胞内源性表达hFcRn，可被视为研究合体滋养层细胞中IgG转运的模型系统。我们在此使用脉冲追踪方案证明，极化的BeWo细胞不仅表现出从顶端到基底外侧的转胞吞作用，还表现出顶端IgG循环。因此，我们首次证明上皮细胞可参与母胎IgG传递和血清IgG水平的调节。将温度从37℃降至16℃会降低但不会阻断IgG循环和转胞吞作用。诺考达唑破坏微管不会影响转胞吞作用或顶端循环。细胞松弛素D使丝状肌动蛋白解聚，刺激顶端内吞作用和循环，而转胞吞作用不受影响。总之，在BeWo细胞中，顶端内化的IgG进入转胞吞和循环途径。虽然转胞吞途径对温度敏感，但独立于微管和肌动蛋白丝，顶端循环途径受温度影响并由肌动蛋白解聚刺激，提示不同的内体亚区室参与转胞吞作用和循环。
