Kertesz Z, Hurst G, Ward M, Willis A C, Caro H, Linton E A, Sargent I L, Redman C W
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, UK.
Placenta. 1999 Jan;20(1):71-9. doi: 10.1053/plac.1998.0351.
The signs of pre-eclampsia are thought to arise from maternal endothelial dysfunction caused by circulating factors of placental origin. Syncytiotrophoblast microvillous membranes (STBM) cause endothelial disruption and inhibit proliferation in vitro. Significantly increased amounts of STBM can be detected in blood from pre-eclamptic women and could contribute to endothelial dysfunction in vivo. This study purified a complex from STBM which inhibits the proliferation of cultured human endothelial cells. Integral membrane proteins were solubilized with sucrose monolaurate. Anion exchange chromatography yielded two peaks of anti-proliferative activity. Only the second peak was specific to STBM and was subjected to further separation by Sephacryl S-200 gel filtration chromatography (GFC). A single peak of specific activity eluted close to the void volume, at a position unaltered by added denaturing agents, guanidium chloride or urea. On Sephacryl S-300 GFC, two peaks were obtained of 410 and 820 kDa, with similar anti-proliferative activity and protein components (by SDS-polyacrylamide gel electrophoresis). The major protein bands were as integrins alpha5 and alpha v, dipeptidyl peptidase IV, alpha-actinin, transferrin, transferrin receptor, placental alkaline phosphatase and monoamine oxidase A.
子痫前期的体征被认为源于胎盘来源的循环因子导致的母体血管内皮功能障碍。合体滋养层微绒毛膜（STBM）可导致内皮细胞破坏并在体外抑制其增殖。在子痫前期女性的血液中可检测到显著增加的STBM量，这可能在体内导致内皮功能障碍。本研究从STBM中纯化出一种抑制培养的人内皮细胞增殖的复合物。用月桂酸蔗糖酯溶解整合膜蛋白。阴离子交换色谱产生了两个抗增殖活性峰。只有第二个峰对STBM具有特异性，并通过Sephacryl S - 200凝胶过滤色谱（GFC）进行进一步分离。一个比活性峰在接近空体积处洗脱，其位置不受添加的变性剂（氯化胍或尿素）影响。在Sephacryl S - 300 GFC上，获得了两个分子量分别为410和820 kDa的峰，具有相似的抗增殖活性和蛋白质成分（通过SDS - 聚丙烯酰胺凝胶电泳）。主要蛋白条带为整合素α5和αv、二肽基肽酶IV、α - 辅肌动蛋白、转铁蛋白、转铁蛋白受体、胎盘碱性磷酸酶和单胺氧化酶A。
