Perforin improves the morphogenesis of mouse placenta disturbed by IL-2 treatment

Perforin improves the morphogenesis of mouse placenta disturbed by IL-2 treatment
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DOI:
10.1016/j.imbio.2004.12.005
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发表时间:
2005-01-01
期刊:
影响因子:
2.8
通讯作者:
Otsuki, Y
Otsuki, Y
中科院分区:
医学4区
文献类型:
--
作者:
Kusakabe, K;Li, ZL;Otsuki, Y

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淋巴细胞产生的成孔蛋白(穿孔素)可以诱导靶细胞凋亡。在小鼠胎盘中,虽然子宫自然杀伤(uNK)细胞产生大量穿孔素,但其在生殖过程中的作用仍不清楚。由于白细胞介素 (IL)-2 可以增强 uNK 细胞的细胞毒性,因此我们研究了在妊娠第 10-14 天接受 IL-2 处理的野生型和穿孔素敲除小鼠胎盘中穿孔素的作用。野生型小鼠的免疫组织化学显示,滋养层糖原细胞膜和 uNK 细胞胞质中穿孔素呈阳性,RT-PCR 分析显示,IL-2 处理后表达水平有所增加,但生育能力没有变化。然而,在IL-2处理的穿孔素敲除小鼠中,活胎数量减少,同时胎盘重量增加。对这些胎盘的检查显示出异常增大的交界区,被大量滋养层糖原细胞和明显少量的凋亡细胞占据。这些发现表明,穿孔素可以通过抑制 IL-2 诱导的交界区过度生长来促进成功妊娠。 (c) 2005 年爱思唯尔有限公司。版权所有。
The pore-forming protein (perforin) produced by lymphocytes can induce apoptosis in target cells. In mouse placenta, although a large amount of perforin is produced by the uterine natural killer (uNK) cells, its role in the reproductive process is still not clear. Since the cytotoxicity of uNK cells can be enhanced by interleukin (IL)-2, we studied the role of perforin in the placenta of wild-type and perforin-knockout mice treated with IL-2 during days 10-14 of pregnancy. Immunohistochemistry of the wild-type mice showed that the perforin was positive in the membrane of trophoblast glycogen cells as well as the cytoplasm of uNK cells, and there was an increase in the expression level following IL-2 treatment as revealed by RT-PCR analysis, although no change was identified in fertility. In the IL-2-treated perforin-knockout mice, however, the number of live fetuses was decreased, accompanied by an increase in the weight of placentae. Examination of these placentae showed an abnormally enlarged junctional zone, occupied by a large number of the trophoblast glycogen cells and significantly few of the apoptotic cells. These findings indicate that perforin can contribute to a successful pregnancy by inhibiting the excessive growth of the junctional zone induced by IL-2. (c) 2005 Elsevier GmbH. All rights reserved.