title: Expression of the human p55 and p75 tumor necrosis factor receptors in primary villous trophoblasts and their role in cytotoxic signal transduction.
abstract: Tumor necrosis factor alpha (TNF alpha) induces the apoptotic death of primary villous cytotrophoblasts in culture (Yui et al., Placenta 1994; 15:819). Since both p55 and p75 TNF receptors (TNFRs) localize to the villous trophoblast, we examined their roles in mediating trophoblast apoptosis. Comparison of 125I-TNF alpha binding competition by receptor-specific antibodies revealed 2.7-fold more TNFRp75 than TNFRp55. Immunohistochemical analysis of receptor distribution showed TNFRp75 to be expressed strongly in < 20% of cells and TNFRp55 moderately in approximately 50%. Culture with TNF alpha increased the percentage of cells expressing TNFRp75 to > 40% but had little effect on TNFRp55 expression. Agonistic anti-TNFRp55 antibody and TNFRp55-specific TNF mutant protein stimulated both apoptosis and loss of trophoblast viability. In contrast, TNFRp75-specific mutant TNF alpha protein failed to induce either of these responses. Furthermore, neither cell death nor apoptosis stimulated by wild-type TNF alpha was inhibited by an antagonistic anti-TNFRp75 antibody. Thus, the apoptotic death of primary cytotrophoblasts is mediated almost entirely by TNFRp55, and the p75 receptor appears to have little effect on the process.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Yui
authors.forename: D
authors.initials: D
authors.lastname: Hemmings
authors.forename: M
authors.initials: M
authors.lastname: Garcia-Lloret
authors.forename: L J
authors.initials: LJ
authors.lastname: Guilbert
mesh_terms: D000906:Antibodies / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D001667:Binding, Competitive; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D007700:Kinetics; D011247:Pregnancy; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis* / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014327:Trophoblasts / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000906:Antibodies; D007457:Iodine Radioisotopes; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha