Chen Q, Viall C, Kang Y, Liu B, Stone P, Chamley L
Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand.
Placenta. 2009 Sep;30(9):767-73. doi: 10.1016/j.placenta.2009.06.008. Epub 2009 Jul 23.
Pre-eclampsia is associated with trophoblast shedding-deportation and endothelial cell dysfunction. Anti-phospholipid autoantibodies increase a women's risk factor of developing pre-eclampsia. In this study we examined the hypothesis that anti-phospholipid antibodies alter the number and nature of trophoblasts shed from the placenta, and that phagocytosis of these altered trophoblasts results in endothelial cell activation. To investigate this we used a placental explant model in which explants were treated with anti-phospholipid antibodies. This treatment resulted in a doubling of the amount of trophoblast shed from the explants. Furthermore, the trophoblasts shed from anti-phospholipid antibody-treated explants were more readily phagocytosed by endothelial cells and subsequently caused the activation of the endothelial cells, as indicated by increased expression of endothelial cell surface ICAM-1 determined by cell-based ELISA, and monocyte adhesion as determined by flow cytometry. Confocal microscopy analysis of trophoblasts shed from anti-phospholipid antibody-treated or control explants demonstrated that anti-phospholipid antibodies, but not control antibodies, were internalised within trophoblasts shed from the explants, and this was accompanied by a reduction in the activity of caspases 3 and 7 in the shed trophoblasts as indicated by FLICA. These results suggest that anti-phospholipid antibodies are selectively transported into trophoblasts where they affect the regulation of the cell cycle leading to excess and aberrant death (necrotic or aponecrotic) and shedding of trophoblasts. If reflected in vivo this might explain, at least in part, how anti-phospholipid antibodies contribute to the pathogenesis of pre-eclampsia.
子痫前期与滋养层细胞脱落-排出及内皮细胞功能障碍有关。抗磷脂自身抗体增加了女性患子痫前期的风险因素。在本研究中，我们检验了以下假设：抗磷脂抗体改变了从胎盘脱落的滋养层细胞的数量和性质，并且这些改变的滋养层细胞的吞噬作用导致内皮细胞活化。为了研究这一点，我们使用了胎盘外植体模型，其中外植体用抗磷脂抗体处理。这种处理导致外植体中脱落的滋养层细胞数量增加了一倍。此外，用抗磷脂抗体处理的外植体脱落的滋养层细胞更容易被内皮细胞吞噬，随后导致内皮细胞活化，这通过基于细胞的酶联免疫吸附测定法测定的内皮细胞表面细胞间黏附分子-1（ICAM-1）表达增加以及通过流式细胞术测定的单核细胞黏附来表明。对用抗磷脂抗体处理或对照的外植体脱落的滋养层细胞进行共聚焦显微镜分析表明，抗磷脂抗体而非对照抗体被外植体脱落的滋养层细胞内化，并且如荧光标记的活性半胱天冬酶检测（FLICA）所示，这伴随着脱落的滋养层细胞中半胱天冬酶3和7活性的降低。这些结果表明，抗磷脂抗体被选择性地转运到滋养层细胞中，在那里它们影响细胞周期的调节，导致滋养层细胞过度和异常死亡（坏死或凋亡坏死）及脱落。如果在体内得到反映，这可能至少部分解释了抗磷脂抗体如何促成子痫前期的发病机制。
