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 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.
Payne
S G
SG
Department of Medical Microbiology and Immunology, The University of Alberta Perinatal Research Centre, University of Alberta, Edmonton, Canada.
Smith
S C
SC
Davidge
S T
ST
Baker
P N
PN
Guilbert
L J
LJ
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D053938:DNA Fragmentation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D019001:Nitric Oxide Synthase