Analysis of p60 and p80 tumor necrosis factor-alpha receptor messenger RNA and protein in human placentas

Tumor necrosis factor-alpha (TNF), a pleiotrophic, multifunctional polypeptide factor, has been reported in both normal and infected human placentas. To identify potential targets for this cytokine, the cells in early and late gestation placentas and extraplacental membranes that express the two TNF receptor (TNF-R) genes, p60 and p80, were identified by using in situ hybridization and immunocytochemistry. Gestation-related, cell lineage-specific differences in steady-state levels of p60 and p80 TNF-R messenger RNA were observed. p60 TNF-R messenger RNA predominated at both early and late stages of gestation, being high in both mesenchymal and trophoblastic cell lineages. By contrast, p80 TNF-R messenger RNA was abundant only in intermittent stretches of first trimester syncytiotrophoblast and term placental mesenchymal cells. Overall, intensities of the TNF-R hybridization signals were stronger in term than in first trimester tissues. Transcription of the two TNF-R genes was confirmed by Northern blot hybridization. Translation was verified in all samples by immunohistology using polyclonal antibodies specific for the receptor proteins. p60 and p80 TNF-R proteins were identified both intracellularly and in maternal and fetal blood. Because TNF-Rs exist in both membrane-bound and soluble forms, the results of this study are consistent with the postulate that placental TNF-R have two critical functions: 1) modulation of TNF utilization by specific placental cell lineages during the course of pregnancy; and 2) protection against excessive TNF produced during infections.