Labor-associated changes in Fas ligand expression and function in human placenta.
Fas ligand (FasL)-dependent apoptosis has been implicated in the control of tissue-damaging inflammatory responses in several immune privileged sites. Here, we present data demonstrating that FasL is expressed on human trophoblast cells throughout pregnancy and transduces growth inhibitory/death signals in cells bearing its receptor, Fas (CD95). Immunohistochemical analysis detected FasL-positive staining in the trophoblast layer of villi of first- and second-trimester and term (no labor) placental tissues, as well as in freshly isolated cytotrophoblasts representing these gestational ages. In contrast, term placental tissues and cytotrophoblasts from labor-associated deliveries exhibited significantly reduced FasL expression, suggesting that parturition altered the characteristics of trophoblast cells. FasL-specific immunoblotting of cytotrophoblast cell lysates further confirmed these results. To assess the functionality of FasL expressed on cytotrophoblasts, we co-cultured these cells with Fas-bearing Jurkat T cells. Cytotrophoblasts from early pregnancy, or term with no labor, significantly inhibited growth in Jurkat cells, evident even at a 1:1 effector:target cell ratio, as determined by the incorporation of [3H]thymidine. Similar results were obtained when a FasL-positive colon carcinoma cell line, SW620, was used in place of cytotrophoblasts. In contrast, term cytotrophoblasts from labor deliveries exhibited poor FasL expression and were quantitatively much less proficient in inhibiting [3H]thymidine incorporation in Jurkat cells. These data indicate that FasL could participate in modulating the inflammatory responses associated with labor and suggest intrinsic molecular differences in the placental microenvironment before and after labor .
Balkundi
D R
DR
Department of Pediatrics, Women and Infants' Hospital of Rhode Island-Brown University, Providence 02905, USA.
Hanna
N
N
Hileb
M
M
Dougherty
J
J
Sharma
S
S
D001483:Base Sequence; D015153:Blotting, Western; D018920:Coculture Techniques; D017931:DNA Primers; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D007743:Labor, Obstetric; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
D017931:DNA Primers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins