Involvement of the Fas ligand and Fas system in apoptosis induction of mouse uterine natural killer cells
Involvement of the Fas ligand and Fas system in apoptosis induction of mouse uterine natural killer cells
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DOI：
10.1262/jrd.16086
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发表时间：
2005-06-01
影响因子：
1.8
通讯作者：
Kiso, Y
中科院分区：
文献类型：
--
作者：
Kusakabe, K;Otsuki, Y;Kiso, Y
已知妊娠子宫中的子宫自然杀伤(Unk)细胞与胎盘的正常发育有关。在小鼠妊娠子宫中，许多Unk细胞在妊娠中期存在，但在妊娠晚期突然减少，并在分娩前几乎消失。我们先前的研究表明，在妊娠晚期，Unk细胞表现出明显的凋亡形态。因此，本研究旨在探讨Fas配体(FasL)和Fas在诱导Unk细胞凋亡中的作用。免疫组织化学结果显示，妊娠晚期Unk细胞表达FasL于胞浆颗粒，Fas表达于细胞膜。在Fas基因缺失的LPR/LPR小鼠中，与野生型小鼠相比，在妊娠晚期明显观察到大量的Unk细胞，而且在妊娠第18天仍有Unk细胞存在，而同期野生型小鼠中Unk细胞很少。在体外培养实验中，野生型胎盘来源的Unk细胞在抗Fas抗体处理后，与对照组相比，经常出现染色质凝集和DNA片段化。这些结果表明，依赖于FasL和Fas的细胞凋亡调节了小鼠妊娠子宫中Unk细胞的细胞形态。
Uterine natural killer (uNK) cells in the pregnant uterus are known to be associated with the normal development of the placenta. In the mouse pregnant uterus, many uNK cells exist during mid pregnancy, although they show a sudden decrease during late pregnancy and almost disappear before delivery. Our previous study indicated that uNK cells showed clear apoptotic morphology during late pregnancy. Therefore, the present study was carried out to define the involvement of Fas ligand (FasL) and Fas in apoptosis induction of uNK cells. Immunohistochemical analyses revealed that uNK cells expressed FasL in the cytoplasmic granules and Fas on the cell membrane during late pregnancy. In lpr/lpr mice, which genetically lack Fas, many uNK cells were clearly observed during late pregnancy compared with wild-type mice, and moreover uNK cells still existed at day-18 of pregnancy, although there were few in wild-type mice during the same period. In the experiment of in vitro culture, uNK cells derived from wild-type placenta showed chromatin condensation and DNA fragmentation frequently following the anti-Fas antibody treatment, as compared with the control. From these results, it is suggested that FasL and Fas-dependent apoptosis regulates cell appearance of uNK cells in the mouse pregnant uterus.