Vishnyakova Polina, Poltavets Anastasiya, Nikitina Maria, Midiber Konstantin, Mikhaleva Liudmila, Muminova Kamilla, Potapova Alena, Khodzhaeva Zulfiya, Pyregov Alexey, Elchaninov Andrey, Fatkhudinov Timur, Sukhikh Gennady
National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 117198 Moscow, Russia.
Histology Department, Peoples' Friendship University of Russia (RUDN University), 117198 Moscow, Russia.
Biomedicines. 2021 Feb 14;9(2):191. doi: 10.3390/biomedicines9020191.
Preeclampsia is a gestation-associated hypertensive syndrome that threatens the life and health of the mother and the child. The condition is presumably caused by systemic failure with a strong involvement of innate immunity. In particular, it has been associated with flexible phenotypes of macrophages, which depend on the molecules circulating in the blood and tissue fluid, such as cytokines and hormones. This study aimed at a comparative evaluation of pro-inflammatory (TNFα) and anti-inflammatory (CD206, MMP9, HGF) markers, as well as the levels of estrogen receptor α, expressed by decidual macrophages in normal pregnancy and in patients with early- and late-onset preeclampsia. The tissue samples of decidua basalis were examined by immunohistochemistry and Western blotting. Isolation of decidual macrophages and their characterization were performed using cultural methods, flow cytometry and real-time PCR. Over 50% of the isolated decidual macrophages were positive for the pan-macrophage marker CD68. In the early-onset preeclampsia group, the levels of estrogen receptor α in decidua were significantly decreased. Furthermore, significantly decreased levels of HGF and CD206 were observed in both preeclampsia groups compared with the control group. The observed downregulation of estrogen receptor α, HGF and CD206 may contribute to the balance of pro- and anti-inflammatory macrophages and thereby to pathogenesis of preeclampsia.
子痫前期是一种与妊娠相关的高血压综合征,威胁着母婴的生命和健康。这种病症可能是由全身性功能衰竭引起的,先天免疫在其中起到了重要作用。特别是,它与巨噬细胞的灵活表型有关,巨噬细胞的表型取决于血液和组织液中循环的分子,如细胞因子和激素。本研究旨在比较评估正常妊娠以及早发型和晚发型子痫前期患者中,由蜕膜巨噬细胞表达的促炎标志物(TNFα)和抗炎标志物(CD206、MMP9、HGF),以及雌激素受体α的水平。通过免疫组织化学和蛋白质印迹法检测了基蜕膜的组织样本。使用培养方法、流式细胞术和实时聚合酶链反应对蜕膜巨噬细胞进行分离和鉴定。超过50%的分离出的蜕膜巨噬细胞对泛巨噬细胞标志物CD68呈阳性。在早发型子痫前期组中,蜕膜中雌激素受体α的水平显著降低。此外,与对照组相比,子痫前期两组中HGF和CD206的水平均显著降低。观察到的雌激素受体α、HGF和CD206的下调可能有助于促炎和抗炎巨噬细胞的平衡,从而导致子痫前期的发病机制。