Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Placenta. 2010 Feb;31(2):106-12. doi: 10.1016/j.placenta.2009.11.011. Epub 2009 Dec 14.
Normal pregnancy is associated with a systemic maternal inflammatory reaction, including the activation of peripheral blood monocytes. This reaction is exaggerated in pre-eclampsia, a severe placenta-dependent disorder of pregnancy specific to humans. It has been suggested that placental syncytiotrophoblast membrane microparticles (STBM), which are released into the peripheral blood, may contribute to the maternal response. The aim of this study was to investigate the inflammatory properties of STBM generated by four different approaches on primary human monocytes in vitro. Cellular viability, phenotype and functional response were analysed. STBM isolated by mechanical dissection and STBM generated from villous explant cultures incubated in hypoxic conditions had only minor influences on the monocytic phenotype and failed to induce a proinflammatory response. By contrast, STBM washed from the maternal side of a placental cotyledon and STBM shed by explants cultured in air up-regulated cell surface expression of the adhesion molecule CD54 and induced the production of interleukin (IL)-8, IL-6 and IL-1beta. Cytokine production was time- and dose-dependent. Our study, therefore, suggests that monocyte activation in normal pregnancy and pre-eclampsia may be induced by STBM released by the placenta. The higher amounts of STBM circulating in maternal blood in pre-eclampsia might lead to the excessive maternal inflammatory reaction.
正常妊娠伴随着全身母体炎症反应,包括外周血单核细胞的激活。这种反应在子痫前期中被夸大,子痫前期是一种严重的、特有的与胎盘相关的人类妊娠疾病。有人提出,胎盘合体滋养层细胞膜微粒(STBM)可能会释放到外周血中,从而促进母体的反应。本研究旨在探讨体外通过四种不同方法产生的 STBM 对原代人单核细胞的炎症特性。分析细胞活力、表型和功能反应。机械分离分离的 STBM 和在低氧条件下孵育的绒毛外植体培养产生的 STBM 对单核细胞表型的影响很小,并且不能诱导促炎反应。相比之下,从胎盘胎盘中冲洗的 STBM 和在空气中培养的外植体脱落的 STBM 上调了细胞表面黏附分子 CD54 的表达,并诱导产生白细胞介素(IL)-8、IL-6 和 IL-1β。细胞因子的产生具有时间和剂量依赖性。因此,我们的研究表明,正常妊娠和子痫前期中单核细胞的激活可能是由胎盘释放的 STBM 诱导的。子痫前期中循环母体血液中 STBM 的数量增加可能导致母体过度炎症反应。