Payne S G, Smith S C, Davidge S T, Baker P N, Guilbert L J
Department of Medical Microbiology and Immunology, The University of Alberta Perinatal Research Centre, University of Alberta, Edmonton, Canada.
Biol Reprod. 1999 May;60(5):1144-50. doi: 10.1095/biolreprod60.5.1144.
Trophoblasts, the fetal cells that line the villous placenta and separate maternal blood from fetal tissue, express both Fas antigen and the tumor necrosis factor (TNF) receptor p55 (TNFRp55), two members of the TNF receptor family that contain a cytoplasmic "death domain" that mediates apoptotic signals. We show that Fas mRNA expressed by cultured villous cytotrophoblasts isolated from term placentas encodes transmembrane sequences and that the protein is full-length (approximately 45 kDa), suggesting that the product is an active plasma membrane-anchored receptor. Its location on the cell surface was confirmed by cellular ELISA analysis of live cells. Although cytotrophoblast apoptosis was induced by TNFalpha, and both anti-Fas antibody (CH11) and FasL-expressing T lymphocyte hybridoma (activated A1.1) cells induced HeLa cell apoptosis, neither CH11 antibody nor activated A1.1 cells stimulated apoptosis in term or first-trimester cytotrophoblasts or in term syncytiotrophoblasts. We conclude that Fas- but not TNFRp55-mediated apoptosis is blocked in primary villous trophoblasts. These data suggest that the Fas response is specifically inactivated by unknown mechanisms to avoid autocrine or paracrine killing by Fas ligand constitutively expressed on neighboring cyto- or syncytiotrophoblasts.
滋养层细胞是衬于绒毛胎盘并将母体血液与胎儿组织分隔开的胎儿细胞，它表达Fas抗原和肿瘤坏死因子（TNF）受体p55（TNFRp55），这是TNF受体家族的两个成员，均含有介导凋亡信号的胞质“死亡结构域”。我们发现，从足月胎盘分离出的培养绒毛细胞滋养层细胞所表达的Fas mRNA编码跨膜序列，且该蛋白为全长蛋白（约45 kDa），这表明该产物是一种有活性的锚定在质膜上的受体。通过对活细胞进行细胞ELISA分析，证实了其在细胞表面的定位。尽管TNFα可诱导细胞滋养层细胞凋亡，抗Fas抗体（CH11）和表达FasL的T淋巴细胞杂交瘤（活化的A1.1）细胞均可诱导HeLa细胞凋亡，但CH11抗体和活化的A1.1细胞均不能刺激足月或孕早期的细胞滋养层细胞或足月合体滋养层细胞发生凋亡。我们得出结论，在原代绒毛滋养层细胞中，Fas介导的凋亡被阻断，但TNFRp55介导的凋亡未被阻断。这些数据表明，Fas反应通过未知机制被特异性失活，以避免被相邻的细胞滋养层细胞或合体滋养层细胞组成性表达的Fas配体进行自分泌或旁分泌杀伤。
