Than Nandor Gabor, Erez Offer, Wildman Derek E, Tarca Adi L, Edwin Samuel S, Abbas Asad, Hotra John, Kusanovic Juan Pedro, Gotsch Francesca, Hassan Sonia S, Espinoza Jimmy, Papp Zoltan, Romero Roberto
Perinatology Research Branch, NICHD, NIH, DHHS, Detroit, Michigan 48201, USA.
J Matern Fetal Neonatal Med. 2008 Jul;21(7):429-42. doi: 10.1080/14767050802041961.
Galectin-1 is a major anti-inflammatory protein expressed by the placenta and immune cells that can bias the character of inflammatory responses toward the Th2 type. Galectin-1 is expressed in immune privileged sites, it can facilitate immune tolerance and tumor immune escape, and it has been successfully used for the suppression of experimental autoimmune diseases as well as graft-versus-host disease in murine models. We propose that an abnormal immune response in some pregnancy complications may be associated with changes in placental expression of galectin-1. To test this hypothesis, we studied placental galectin-1 mRNA and protein expression and localization in women with preeclampsia (PE) and in those who delivered a small-for-gestational age (SGA) neonate.
This cross-sectional study included pregnant women matched for gestational age at delivery in the following groups: (1) severe PE (n = 10), (2) severe PE complicated with SGA (n = 10), (3) SGA without PE (n = 10), and (4) controls (n = 10). Galectin-1 mRNA and protein were localized in placentas by in situ hybridization and immunofluorescence microscopy. Galectin-1 mRNA expression was determined by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), and galectin-1 protein content by Western blot. Non-parametric statistics were used for analysis.
(1) In normal term placentas, galectin-1 mRNA or immunofluorescence signals were detected in the trophoblasts, villous stromal cells, Hofbauer cells, endothelial cells of the villous blood vessels, and the villous stroma. (2) Placental galectin-1 mRNA expression was significantly higher in severe PE (with or without SGA) than in controls (1.47-fold, p = 0.004; 1.44-fold, p = 0.003, respectively) and in SGA (1.68-fold, p = 0.001; 1.64-fold, p = 0.001, respectively). (3) Trophoblasts in placentas of patients with severe PE had the most intense galectin-1 immunostaining.
(1) We report for the first time the placental expression and localization of galectin-1 mRNA and demonstrate that the protein is abundantly present in third trimester human placentas. (2) Placental galectin-1 expression is higher in severe PE than in normal pregnancy regardless of the presence of SGA. (3) However, it is not altered in SGA without PE. We propose that the increased placental expression of galectin-1 in patients with severe PE may represent a fetal response to an exaggerated systemic maternal inflammation; thus, galectin-1 may be implicated in maternal-fetal immune tolerance in humans.
半乳糖凝集素-1是一种主要由胎盘和免疫细胞表达的抗炎蛋白,可使炎症反应偏向Th2型。半乳糖凝集素-1在免疫特惠部位表达,可促进免疫耐受和肿瘤免疫逃逸,并且已成功用于抑制小鼠模型中的实验性自身免疫性疾病以及移植物抗宿主病。我们提出,某些妊娠并发症中异常的免疫反应可能与胎盘半乳糖凝集素-1表达的变化有关。为验证这一假设,我们研究了子痫前期(PE)患者以及分娩小于胎龄(SGA)新生儿的产妇胎盘半乳糖凝集素-1 mRNA和蛋白的表达及定位。
这项横断面研究纳入了以下几组在分娩时孕周匹配的孕妇:(1)重度PE(n = 10),(2)重度PE合并SGA(n = 10),(3)无PE的SGA(n = 10),以及(4)对照组(n = 10)。通过原位杂交和免疫荧光显微镜将半乳糖凝集素-1 mRNA和蛋白定位在胎盘中。通过定量实时逆转录-聚合酶链反应(RT-PCR)测定半乳糖凝集素-1 mRNA表达,通过蛋白质印迹法测定半乳糖凝集素-1蛋白含量。采用非参数统计进行分析。
(1)在足月正常胎盘中,在滋养层细胞、绒毛基质细胞、霍夫鲍尔细胞、绒毛血管内皮细胞和绒毛基质中检测到半乳糖凝集素-1 mRNA或免疫荧光信号。(2)重度PE(无论有无SGA)患者胎盘半乳糖凝集素-1 mRNA表达均显著高于对照组(分别为1.47倍,p = 0.004;1.44倍,p = 0.003)和SGA组(分别为1.68倍,p = 0.001;1.64倍,p = 0.001)。(3)重度PE患者胎盘的滋养层细胞半乳糖凝集素-1免疫染色最强。
(1)我们首次报道了半乳糖凝集素-1 mRNA在胎盘的表达及定位,并证明该蛋白在孕晚期人胎盘中大量存在。(2)无论有无SGA,重度PE患者胎盘半乳糖凝集素-1表达均高于正常妊娠。(3)然而,无PE的SGA患者其表达未改变。我们提出,重度PE患者胎盘半乳糖凝集素-1表达增加可能代表胎儿对母体全身性过度炎症的一种反应;因此,半乳糖凝集素-1可能参与了人类母婴免疫耐受。