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 m aternal blood from fetal tissue, express both Fas antigen and the tumor nec rosis factor (TNF) receptor p55 (TNFRp55), two members of the TNF receptor family that contain a cytoplasmic "death domain" that mediates apoptotic si gnals. 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 su rface was confirmed by cellular ELISA analysis of live cells. Although cyto trophoblast apoptosis was induced by TNF alpha, and both anti-Fas antibody (CH11) and Fast-expressing T lymphocyte hybridoma (activated A1.1) cells in duced HeLa cell apoptosis, neither CH11 antibody nor activated A1.1 cells s timulated apoptosis in term or first-trimester cytotrophoblasts or in term syncytiotrophoblasts, We conclude that Fas- but not TNFRp55-mediated apopto sis is blocked in primary villous trophoblasts, These data suggest that the Fas response is specifically inactivated by unknown mechanisms to avoid au tocrine or paracrine killing by Fas ligand constitutively expressed on neig hboring cyto- or syncytiotrophoblasts.