The Implication of Aberrant GM-CSF Expression in Decidual Cells in the Pathogenesis of Preeclampsia
The Implication of Aberrant GM-CSF Expression in Decidual Cells in the Pathogenesis of Preeclampsia
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DOI：
10.2353/ajpath.2010.091247
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发表时间：
2010-11-01
影响因子：
6
通讯作者：
Lockwood, Charles J.
中科院分区：
文献类型：
--
作者：
Huang, S. Joseph;Zenclussen, Ana C.;Lockwood, Charles J.
先兆子痫的特点是全身炎症状态夸大，胎盘浅。在蜕膜着床部位，子痫前期伴有大量的巨噬细胞和树突状细胞及其募集的趋化因子，参与了血管内滋养细胞侵袭的损害。已知粒细胞-巨噬细胞集落刺激因子调节巨噬细胞和树突状细胞的分化，促使在体内和体外评估人蜕膜和先兆子痫小鼠模型中粒细胞-巨噬细胞集落刺激因子的表达。这项研究揭示了子痫前期蜕膜中粒细胞-巨噬细胞集落刺激因子表达水平的增加。此外，肿瘤坏死因子-α和白介素1-β，这两种与先兆子痫的发生有关的细胞因子，都显著上调了培养的早期妊娠人类蜕膜细胞中粒细胞-巨噬细胞集落刺激因子的产生。这些培养物的条件培养液促进巨噬细胞和树突状细胞从单核细胞前体分化。对子痫前期小鼠模型的评估显示，与对照动物相比，受影响动物的蜕膜显示出更高水平的免疫反应性粒细胞-巨噬细胞集落刺激因子，以及巨噬细胞和树突状细胞的数量增加。由于粒细胞-巨噬细胞集落刺激因子是巨噬细胞和树突状细胞分化和激活的有效诱导剂，这些发现表明该因子在子痫前期的发病机制中起着关键作用。(Am J Pathol2010,177：2472-2482；DOI：10.2353/ajpath.2010.091247)
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-alpha and interleukin-1 beta, 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. (Am J Pathol 2010, 177:2472-2482; DOI: 10.2353/ajpath.2010.091247)