Human placental indoleamine 2,3-dioxygenase: cellular localization and characterization of an enzyme preventing fetal rejection
Human placental indoleamine 2,3-dioxygenase: cellular localization and characterization of an enzyme preventing fetal rejection
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DOI：
10.1016/s0925-4439(99)00096-4
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发表时间：
2000-01-03
影响因子：
6.2
通讯作者：
Boyd, CAR
中科院分区：
文献类型：
--
作者：
Kudo, Y;Boyd, CAR
为了验证(Munn，周，Attwood，Bondarev，Conway，Matt，Brown，Mellor，Science 281(1998)1191-1193)胎盘色氨酸分解代谢阻止哺乳动物胎儿免疫排斥的假说，我们研究了胎盘吲哚胺2，3-双加氧酶(EC 1.13.11.42)的细胞定位和特性。采用差速和不连续蔗糖梯度离心法对吲哚胺2，3-双加氧酶活性进行了定量测定。在分离的胎盘合体滋养层细胞刷状缘微绒毛质膜中寻找酶活性。我们发现，这种膜制剂(相对于膜标志酶碱性磷酸酶(EC 3.1.3.1)的活性，其纯度是起始匀浆的32.4倍)被吲哚胺2，3-双加氧酶(其比活性降低了25%)强烈地负浓缩。因此，胎盘吲哚胺2，3-双加氧酶在合体滋养细胞的母体面对刷状缘膜中不表达。1-甲基-DL-色氨酸，Munn等人使用。作为抑制吲哚胺2，3-双加氧酶的关键实验工具，L-色氨酸对人胎盘吲哚胺2，3-双加氧酶具有竞争性抑制作用。因此，这一假设基于在小鼠身上进行的实验，可能适用于避免人类怀孕期间胎儿的免疫排斥。(C)2000 Elsevier Science B.V.保留所有权利。
In order to test the hypothesis (Munn, Zhou, Attwood, Bondarev, Conway, Marshall, Brown, Mellor, Science 281 (1998) 1191-1193) that localized placental tryptophan catabolism prevents immune rejection of the mammalian fetus, the cellular localization and characteristics of human placental indoleamine 2,3-dioxygenase (EC 1.13.11.42) were studied. The localization of indoleamine 2,3-dioxygenase activity was determined quantitatively using cell fractionation by differential and discontinuous sucrose gradient centrifugation. Enzyme activity was looked for in isolated brush border microvillous plasma membranes of placental syncytiotrophoblast. We found that this membrane preparation (which showed a 32.4-fold purification from the starting homogenate with reference to the activity of a membrane marker enzyme, alkaline phosphatase (EC 3.1.3.1)) was strongly negatively enriched with indoleamine 2,3-dioxygenase (which showed a one twenty-fifth decrease in its specific activity). Placental indoleamine 2,3-dioxygenase is thus not expressed in the maternal facing brush border membrane of syncytiotrophoblast. 1-Methyl-DL-tryptophan which was used by Munn et al. as a key experimental tool for inhibiting indoleamine 2,3-dioxygenase in the murine model showed a competitive inhibition of human placental indoleamine 2,3-dioxygenase with L-tryptophan. The hypothesis, based on experiments performed in mouse, may therefore be applicable to avoidance of immune rejection of the fetus in human pregnancy. (C) 2000 Elsevier Science B.V. All rights reserved.