Natural killer cells in the pathogenesis of preeclampsia: a double-edged sword
Natural killer cells in the pathogenesis of preeclampsia: a double-edged sword
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DOI：
10.1080/14767058.2020.1740675
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发表时间：
2020-03-18
影响因子：
1.8
通讯作者：
Li, Liping
中科院分区：
文献类型：
--
作者：
Du, Mingyue;Wang, Weijia;Li, Liping
目的：探讨自然杀伤（NK）细胞、绒毛外滋养层细胞（EVT）与妊娠早期血管重构的关系及NK细胞与妊娠晚期子痫前期（PE）的关系。研究方法：收集正常妊娠妇女的人蜕膜组织，用免疫组织化学方法检测NK细胞与子宫血管重塑的关系。采用流式细胞术检测正常妊娠、晚发型和早发性PE患者外周血NK（pNK）和蜕膜NK（dNK）细胞的数量及细胞内IFN-γ、穿孔素和颗粒酶B的水平。检查了正常和PE妊娠的dNK细胞的细胞溶解功能。检测了正常妊娠和PE妊娠dNK细胞条件培养液（CM）对妊娠早期滋养细胞侵袭和迁移的影响。结果如下：在妊娠早期样本（妊娠9-13周）中，我们注意到中度血管重塑，血管周围NK细胞丰富，但周围EVT数量有限。人pNK细胞和dNK细胞的数量和细胞内干扰素（IFN）-γ，穿孔素和颗粒酶B的生产显着高于PE与正常妊娠在交付的时间为早发性和迟发性疾病。与正常对照组相比，PE妊娠的dNK细胞不仅杀死早期妊娠滋养层细胞，而且还抑制其侵袭和迁移。结论：我们的研究结果表明，NK细胞，与EVT，可能发挥重要作用，在控制子宫SA重塑血管重塑的早期阶段，但他们有助于PE的发病机制在妊娠晚期。
Objective: To investigate the relationship between natural killer (NK) cells, extravillous trophoblast cells (EVTs) and vessel remodeling in early human pregnancy, and the association between NK cells and preeclampsia (PE) in late human pregnancy. Methods: Human decidual tissues from women with normal pregnancies were collected and examined for the relationship of NK cells with uterine vessel remodeling using immunohistochemistry. Percentages of peripheral blood NK (pNK) and decidual NK (dNK) cells and the levels of intracellular interferon (IFN)-gamma, perforin and granzyme B in normal pregnancies, late-onset and early-onset PE were analyzed using flow cytometry. Cytolytic functions of dNK cells from normal and PE pregnancies were examined. Effects of conditioned medium (CM) of dNK cells from normal and PE pregnancies on first trimester trophoblast invasion and migration were tested. Results: In early pregnancy samples (9-13 weeks of gestation), we noted moderate vessel remodeling with abundant perivascular NK cells but a limited number of surrounding EVTs. The numbers of both human pNK cells and dNK cells and intracellular interferon (IFN)-gamma, perforin and granzyme B production were significantly higher in PE compared with normal pregnancies at the time of delivery for both early- and late-onset disease. dNK cells from PE pregnancies not only killed first trimester trophoblasts but also inhibited their invasion and migration when compared to normal controls. Conclusion: Our results suggest that NK cells, in conjunction with EVTs, may play an important role in controlling uterine SA remodeling at the early stages of vessel remodeling, but they contribute to the pathogenesis of PE in late pregnancy.