Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208063, New Haven, CT 06520-8063, USA.
Am J Pathol. 2010 Nov;177(5):2472-82. doi: 10.2353/ajpath.2010.091247. Epub 2010 Sep 9.
Preeclampsia is characterized by an exaggerated systemic inflammatory state as well as shallow placentation. In the decidual implantation site, preeclampsia is accompanied by an excessive number of both macrophages and dendritic cells as well as their recruiting chemokines, which have been implicated in the impairment of endovascular trophoblast invasion. Granulocyte-macrophage colony-stimulating factor is known to regulate the differentiation of both macrophages and dendritic cells, prompting both in vivo and in vitro evaluation of granulocyte-macrophage colony-stimulating factor expression in human decidua as well as in a mouse model of preeclampsia. This study revealed increased granulocyte-macrophage colony-stimulating factor expression levels in preeclamptic decidua. Moreover, both tumor necrosis factor-α and interleukin-1 β, cytokines that are implicated in the genesis of preeclampsia, markedly up-regulated granulocyte-macrophage colony-stimulating factor production in cultured first-trimester human decidual cells. The conditioned media of these cultures promoted the differentiation of both macrophages and dendritic cells from a monocyte precursor. Evaluation of a murine model of preeclampsia revealed that the decidua of affected animals displayed higher levels of immunoreactive granulocyte-macrophage colony-stimulating factor as well as increased numbers of both macrophages and dendritic cells when compared to control animals. Because granulocyte-macrophage colony-stimulating factor is a potent inducer of differentiation and activation of both macrophages and dendritic cells, these findings suggest that this factor plays a crucial role in the pathogenesis of preeclampsia.
子痫前期的特征是全身性炎症反应过度以及胎盘着床浅。在蜕膜植入部位，子痫前期伴随着大量的巨噬细胞和树突状细胞及其募集趋化因子，这些细胞和趋化因子被认为参与了血管内滋养细胞侵袭的损害。粒细胞-巨噬细胞集落刺激因子（granulocyte-macrophage colony-stimulating factor，GM-CSF）已知可调节巨噬细胞和树突状细胞的分化，这促使人们对人蜕膜和子痫前期小鼠模型中的 GM-CSF 表达进行了体内和体外评估。本研究揭示了子痫前期蜕膜中 GM-CSF 表达水平升高。此外，肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和白细胞介素-1β（interleukin-1β，IL-1β）这两种与子痫前期发生有关的细胞因子，明显上调了培养的人早孕蜕膜细胞中 GM-CSF 的产生。这些培养物的条件培养基促进了单核细胞前体向巨噬细胞和树突状细胞的分化。对子痫前期小鼠模型的评估显示，与对照动物相比，受影响动物的蜕膜中 GM-CSF 的免疫反应性水平更高，且巨噬细胞和树突状细胞的数量也增加。由于 GM-CSF 是巨噬细胞和树突状细胞分化和激活的有力诱导剂，这些发现表明该因子在子痫前期的发病机制中起关键作用。
