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Biology of Reproduction 60, 1144-1150 (1999)
©Copyright 1999 Society for the Study of Reproduction, Inc.

Death Receptor Fas/Apo-1/CD95 Expressed by Human Placental Cytotrophoblasts Does Not Mediate Apoptosis1

Shawn G. Payne3,a, Steve C. Smith3,d, Sandra T. Davidgeb,c, Phillip N. Bakerd, and Larry J. Guilbert2,a,c

a Departments of Medical Microbiology and Immunology and b Obstetrics and Gynecology, c The University of Alberta Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2H7 d Department of Obstetrics, City Hospital, University of Nottingham, Nottingham, NG7 2UH, United Kingdom

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 TNF{alpha}, 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.

1 Supported by grants from the Toronto Sick Children's Hospital Foundation (L.J.G.), the University of Alberta Hospital Foundation (L.J.G.), and an interlaboratory collaboration grant from the Wellcome Trust (P.N.B. and S.T.D.). S.P. is supported by an Alberta Heritage for Medical Research Studentship, and S.S. is a Wellbeing training fellow.

2 Correspondence: Larry J. Guilbert, Dept. Medical Microbiology and Immunology, 1–41 Medical Sciences Building, University of Alberta, Edmonton, AB, Canada T6G 2H7. FAX: 403 492 9828; larry.guilbert{at}ualberta.ca

3 S. Payne and S. Smith contributed equally to this publication and are co-first authors.




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