Balkundi D R, Hanna N, Hileb M, Dougherty J, Sharma S
Department of Pediatrics, Women and Infants' Hospital of Rhode Island-Brown University, Providence 02905, USA.
Pediatr Res. 2000 Mar;47(3):301-8. doi: 10.1203/00006450-200003000-00004.
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 .
Fas配体（FasL）依赖性凋亡与几个免疫豁免部位组织损伤性炎症反应的控制有关。在此，我们展示的数据表明，FasL在整个孕期的人滋养层细胞上表达，并在携带其受体Fas（CD95）的细胞中传导生长抑制/死亡信号。免疫组织化学分析在孕早期、孕中期和足月（未临产）胎盘组织绒毛的滋养层中检测到FasL阳性染色，以及在代表这些孕周的新鲜分离的细胞滋养层中也检测到。相反，来自临产相关分娩的足月胎盘组织和细胞滋养层显示FasL表达显著降低，表明分娩改变了滋养层细胞的特性。细胞滋养层细胞裂解物的FasL特异性免疫印迹进一步证实了这些结果。为了评估细胞滋养层上表达的FasL的功能，我们将这些细胞与携带Fas的Jurkat T细胞共培养。孕早期或足月未临产的细胞滋养层显著抑制Jurkat细胞的生长，即使在效应细胞：靶细胞比例为1:1时也很明显，这通过[3H]胸腺嘧啶核苷掺入来确定。当使用FasL阳性结肠癌细胞系SW620代替细胞滋养层时，获得了类似的结果。相反，来自临产分娩的足月细胞滋养层显示FasL表达较差，并且在抑制Jurkat细胞中[3H]胸腺嘧啶核苷掺入方面在数量上也不那么有效。这些数据表明FasL可能参与调节与分娩相关的炎症反应，并提示分娩前后胎盘微环境存在内在分子差异。
