TRAIL (Apo-2L) and TRAIL receptors in human placentas: implications for immune privilege
| Autor: | T A, Phillips, J, Ni, G, Pan, S M, Ruben, Y F, Wei, J L, Pace, J S, Hunt |
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| Rok vydání: | 1999 |
| Předmět: |
Cytotoxicity
Immunologic Membrane Glycoproteins Tumor Necrosis Factor-alpha Macrophages Placenta Receptors Tumor Necrosis Factor Cell Line Trophoblasts TNF-Related Apoptosis-Inducing Ligand Interferon-gamma Pregnancy Trimester First Pregnancy Immune Tolerance Humans Female RNA Messenger Apoptosis Regulatory Proteins |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 162(10) |
| ISSN: | 0022-1767 |
| Popis: | Mechanisms accounting for protection of the fetal semiallograft from maternal immune cells remain incompletely understood. In other contexts, interactions between TRAIL (TNF-related apoptosis-inducing ligand/Apo-2L) and its receptors kill activated lymphocytes. The purpose of this study was therefore to investigate the potential of the TRAIL/TRAIL-R system to protect the placenta against immune cell attack. Analysis by Northern blotting demonstrated mRNAs encoding TRAIL as well as the four TRAIL receptors (DR4, DR5, DcR1/TRID, DcR2/TRUNDD) in human placentas. Immunohistochemical experiments demonstrated that TRAIL protein is prominent in syncytiotrophoblast, an uninterrupted placental cell layer that is continuously exposed to maternal blood, as well as in macrophage-like placental mesenchymal cells (Hofbauer cells). Studies on cell lines representing trophoblasts (Jar, JEG-3 cells) and macrophages (U937, THP-1 cells) showed that both lineages contained TRAIL mRNA and that steady state levels of transcripts were increased 2- to 11-fold by IFN-gamma. By contrast, cell lineage-specific differences were observed in expression of the TRAIL-R genes. Although all four lines contained mRNA encoding the apoptosis-inducing DR5 receptor, only trophoblast cells contained mRNA encoding the DcR1 decoy receptor and only macrophages contained DcR2 decoy receptor transcripts. DR4 mRNA was present only in THP-1 cells and was the only TRAIL-R transcript increased by IFN-gamma. Cytotoxicity assays revealed that the two trophoblast cell lines were resistant, whereas the two macrophage lines were partially susceptible to killing by rTRAIL. Collectively, the results are consistent with a role for the TRAIL/TRAIL-R system in the establishment of placental immune privilege. |
| Databáze: | OpenAIRE |
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