Impaired decidual natural killer cell regulation of vascular remodelling in early human pregnancies with high uterine artery resistance.
Impaired decidual natural killer cell regulation of vascular remodelling in early human pregnancies with high uterine artery resistance.
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在子宫耐药性高的早期人类妊娠中，血管重塑的决定性自然杀伤细胞调节受损。
DOI：
10.1002/path.4057
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发表时间：
2012-11
影响因子：
7.3
通讯作者：
Cartwright, Judith E.
中科院分区：
文献类型：
--
作者：
Fraser, Rupsha;Whitley, Guy Stj;Johnstone, Alan P.;Host, Amanda J.;Sebire, Neil J.;Thilaganathan, Baskaran;Cartwright, Judith E.
在人类妊娠期间，自然杀伤（NK）细胞在母体蜕膜中积累，但其具体作用仍有待确定。在滋养层浸润和子宫螺旋动脉重塑过程中，存在蜕膜NK（dNK）细胞。这些事件对于成功的胎盘形成和为发育中的胎儿提供充足的血液供应至关重要。危险的妊娠并发症先兆子痫中螺旋动脉重塑受损。我们研究了从妊娠9-14周的孕妇中分离的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侵袭行为，部分通过HGF。从具有较高抵抗指数的妊娠中分离的细胞不太能够做到这一点，并且分泌较少的促侵袭因子。来自具有正常阻力指数的妊娠的dNK细胞可以诱导体外血管平滑肌和内皮细胞的凋亡变化，这是血管重塑中的重要事件，部分通过Fas信号传导。从高抵抗指数妊娠中分离的dNK细胞不能诱导血管凋亡，并且分泌较少的促凋亡因子。我们模拟了母胎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。一个潜在的机制，有助于受损的血管重塑妊娠子宫动脉阻力较高。这些发现可能有助于确定细胞相互作用的病理妊娠障碍，其中重塑受损，如先兆子痫。版权所有© 2012大不列颠及爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
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. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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