Expression of the Human p55 and p75 Tumor Necrosis Factor Receptors in Primary Villous Trophoblasts and Their Role in Cytotoxic Signal Transduction1

Autor: Denise G. Hemmings, Larry J. Guilbert, Jane Yui, M. Garcia-Lloret
Rok vydání: 1996
Předmět:
Zdroj: Biology of Reproduction. 55:400-409
ISSN: 1529-7268
0006-3363
DOI: 10.1095/biolreprod55.2.400
Popis: 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 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.
Databáze: OpenAIRE