Localisation of indoleamine 2,3-dioxygenase and kynurenine hydroxylase in the human placenta and decidua: Implications for role of the kynurenine pathway in pregnancy
Localisation of indoleamine 2,3-dioxygenase and kynurenine hydroxylase in the human placenta and decidua: Implications for role of the kynurenine pathway in pregnancy
复制标题
DOI：
10.1016/j.placenta.2004.08.009
复制
发表时间：
2005-07-01
期刊：
影响因子：
3.8
通讯作者：
Walker, D
中科院分区：
文献类型：
--
作者：
Ligam, P;Manuelpillai, U;Walker, D
吲哚胺2,3-双加氧酶（IDO）与妊娠早期的免疫耐受有关，但胎盘中存在产生其他生物活性犬尿氨酸终产物的酶mrna，这表明犬尿氨酸途径代谢物具有其他功能。本研究的目的是研究两个关键酶- IDO和犬尿氨酸羟化酶(kyn - oase) -在妊娠早期蜕膜和人类胎盘中的定位。免疫细胞化学结果显示，IDO和kyn - oase在孕早期蜕膜间质和腺上皮细胞中表达强烈。在妊娠早期和中期胎盘中，IDO和kyn - oase定位于合体滋养细胞、间质细胞和巨噬细胞。IDO和kyn - oase mrna也被鉴定出来，这些酶似乎是有功能的，因为当孕早期胎盘外植体在培养中保持48小时时，犬尿氨酸和3-羟基邻氨基苯酸（这些酶各自的活性产物）被释放到培养基中。在胎盘中，IDO和kyn - oase的免疫反应主要局限于绒毛血管的血管内皮细胞和胎儿绒毛内的巨噬细胞。而合胞体染色很弱或不存在。这些酶的表达从合体滋养细胞转移到末端绒毛的胎儿内皮细胞表明，这些酶的功能可能从妊娠早期在母胎界面的免疫抑制作用转变为妊娠后期与胎胎盘血流或胎盘代谢调节相关的功能。(c) 2005 Elsevier Ltd版权所有。
Indoleamine 2,3-dioxygenase (IDO) has been implicated in contributing to immunotolerance in early pregnancy, but the presence in the term placenta of mRNAs for enzymes that produce other biologically active kynurenine end-products suggests other functions for kynurenine pathway metabolites. The aim of this study was to investigate the localisation of two key enzymes - IDO and kynurenine hydroxylase (KYN-OHase) - in first trimester decidua and in the human placenta across pregnancy. Using immunocytochemistry, it was shown that there was strong expression of IDO and KYN-OHase in stromal and glandular epithelial cells of first trimester decidua. In first and second trimester placenta, IDO and KYN-OHase were localised to the syncytiotrophoblast, stroma and macrophages. IDO and KYN-OHase mRNAs were also identified, and the enzymes appear to be functional because kynurenine and 3-hydroxy-anthranilic acid (respective products of the activity of these enzyme) were released into the medium when first trimester placental explants were maintained in culture for 48 h. In term placenta, both IDO and KYN-OHase immunoreactivities were confined mainly to vascular endothelial cells of villous blood vessels, and to macrophages within the fetal villus, whereas syncytial staining was very weak or absent. The shift of expression of these enzymes away from the syncytiotrophoblast to fetal endothelial cells in terminal villi suggests that the function of the enzymes may change from a role in immunosuppression at the maternal-fetal interface in early pregnancy, to one associated with regulation of fetoplacental blood flow or placental metabolism in late gestation. (c) 2005 Elsevier Ltd. All rights reserved.