Division of Biomedical Sciences, St George's, University of London, London, UK.
J Pathol. 2012 Nov;228(3):322-32. doi: 10.1002/path.4057. Epub 2012 Jul 18.
During human pregnancy, natural killer (NK) cells accumulate in the maternal decidua, but their specific roles remain to be determined. Decidual NK (dNK) cells are present during trophoblast invasion and uterine spiral artery remodelling. These events are crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Remodelling of spiral arteries is impaired in the dangerous pregnancy complication pre-eclampsia. We studied dNK cells isolated from pregnancies at 9-14 weeks' gestation, screened by uterine artery Doppler ultrasound to determine resistance indices which relate to the extent of spiral artery remodelling. dNK cells were able to promote the invasive behaviour of fetal trophoblast cells, partly through HGF. Cells isolated from pregnancies with higher resistance indices were less able to do this and secreted fewer pro-invasive factors. dNK cells from pregnancies with normal resistance indices could induce apoptotic changes in vascular smooth muscle and endothelial cells in vitro, events of importance in vessel remodelling, partly through Fas signalling. dNK cells isolated from high resistance index pregnancies failed to induce vascular apoptosis and secreted fewer pro-apoptotic factors. We have modelled the cellular interactions at the maternal-fetal interface and provide the first demonstration of a functional role for dNK cells in influencing vascular cells. A potential mechanism contributing to impaired vessel remodelling in pregnancies with a higher uterine artery resistance is presented. These findings may be informative in determining the cellular interactions contributing to the pathology of pregnancy disorders where remodelling is impaired, such as pre-eclampsia.
在人类妊娠期间，自然杀伤 (NK) 细胞会在母体蜕膜中积累，但它们的具体作用仍有待确定。蜕膜 NK(dNK) 细胞存在于滋养层浸润和子宫螺旋动脉重塑过程中。这些事件对于成功的胎盘形成和向发育中的胎儿提供充足的血液供应至关重要。螺旋动脉重塑在危险的妊娠并发症子痫前期中受损。我们研究了从妊娠 9-14 周分离的 dNK 细胞，通过子宫动脉多普勒超声进行筛选，以确定与螺旋动脉重塑程度相关的阻力指数。dNK 细胞能够促进胎儿滋养层细胞的浸润行为，部分通过 HGF。从阻力指数较高的妊娠中分离的细胞，其促进能力较弱，分泌的促浸润因子较少。来自阻力指数正常妊娠的 dNK 细胞能够在体外诱导血管平滑肌和内皮细胞发生凋亡变化，这是血管重塑的重要事件，部分通过 Fas 信号传导。从高阻力指数妊娠中分离的 dNK 细胞未能诱导血管凋亡，并且分泌的促凋亡因子较少。我们已经模拟了母体-胎儿界面的细胞相互作用，并首次证明了 dNK 细胞在影响血管细胞方面的功能作用。提出了一种潜在的机制，该机制可能导致具有较高子宫动脉阻力的妊娠中血管重塑受损。这些发现可能有助于确定在重塑受损的妊娠疾病（如子痫前期）中导致病理的细胞相互作用。
