Death receptor Fas/Apo-1/CD95 expressed by human placental cytotrophoblasts does not mediate apoptosis

Trophoblasts, the fetal cells that line the villous placenta and separate maternal blood from fetal tissue, express both Fas an-tigen and the tumor necrosis factor (TNF) receptor p55 (TNFRp55), two members of the TNF receptor family that con-tain a cytoplasmic ‘‘death domain’ ’ that mediates apoptotic sig-nals. We show that Fas mRNA expressed by cultured villous cy-totrophoblasts isolated from term placentas encodes transmem-brane sequences and that the protein is full-length (approxi-mately 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 TNFa, and both anti-Fas antibody (CH11) and FasL-expressing T lymphocyte hybrid-oma (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 syncytiotro-phoblasts. We conclude that Fas- but not TNFRp55-mediated ap-optosis is blocked in primary villous trophoblasts. These data suggest that the Fas response is specifically inactivated by un-known mechanisms to avoid autocrine or paracrine killing by Fas ligand constitutively expressed on neighboring cyto- or syn-cytiotrophoblasts