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免疫细胞化学研究在怀孕期的小鼠中,UNK 细胞及其细胞外基质配体上的黏附分子。

Immunocytochemical studies of adhesion molecules on mouse UNK cells and their extracellular matrix ligands during mouse pregnancy.

机构信息

Department of Biomedical Science, UNIFAL-MG, Alfenas, Minas Gerais, Brazil.

出版信息

Anat Rec (Hoboken). 2010 Jun;293(6):1081-8. doi: 10.1002/ar.21117.

Abstract

Uterine natural killer (uNK) cells are the dominant lymphocytes of pregnant mammals' uterus. Studies have identified four differentiation stage of mouse uNK cells based on Dolichos biflorus lectin cytochemistry, and their distribution showed preferential domain in the uterus through out the pregnancy. This work was done to investigate the expression of alpha5, alpha6, and beta7 integrins on uNK cells and their ligands distribution. Section of mouse uterus from sixth to seventeenth gestational days were submitted to immunocytochemistry and positive reactions for alpha5, alpha6, and beta7 integrins were found on uNK from eighth to tenth gestational days but not after twelfth gestational days. Fibronectin reactions were seemed from sixth to tenth gestational days around uNK from the myometrium and endometrium close to the myometrium. No reaction for fibronectin was seen in the decidualized and nondecidualized endometrium near the placenta. Laminin reaction was seen just in the antimesometrial side. beta7 integrin seems to be the active receptor to bind with VCAM-1 or MAdCAM-1 of endothelial cells, promoting the uNK cross through the vessels. The absence of laminin in an uNK domain suggests these cells are not dependent of laminin and alpha6 integrin for their establishment. However, fibronectin seems to support uNK migration, proliferation, differentiation, and survival in the uterus by binding with alpha5 integrin. The loss of alpha5 integrin ligation by the down regulation of fibronectin could inhibits these events and further studies are need to investigate whether unligated alpha5 can actively and initiate apoptosis, maybe in a caspase 8-dependent way that has been called integrin-mediated death.

摘要

子宫自然杀伤 (uNK) 细胞是妊娠哺乳动物子宫中占主导地位的淋巴细胞。研究根据双花扁豆凝集素细胞化学将小鼠 uNK 细胞分为四个分化阶段,其分布在整个妊娠过程中表现出对子宫的优先域。这项工作旨在研究 uNK 细胞上 α5、α6 和 β7 整合素及其配体的分布。从第六天到第十七天的妊娠小鼠子宫切片进行免疫细胞化学染色,发现 α5、α6 和 β7 整合素在第八天到第十天的 uNK 上呈阳性反应,但在第十二天之后没有。从第六天到第十天,在靠近子宫肌层的子宫肌层和子宫内膜周围的 uNK 上可以看到纤维连接蛋白的反应。靠近胎盘的蜕膜化和非蜕膜化子宫内膜没有纤维连接蛋白反应。层粘连蛋白反应仅见于反系膜侧。β7 整合素似乎是与血管内皮细胞上的 VCAM-1 或 MAdCAM-1 结合的活性受体,促进 uNK 通过血管迁移。uNK 域中缺乏层粘连蛋白表明这些细胞不依赖于层粘连蛋白和 α6 整合素来建立。然而,纤维连接蛋白通过与 α5 整合素结合,似乎支持 uNK 在子宫中的迁移、增殖、分化和存活。纤维连接蛋白下调导致 α5 整合素结合减少,可能抑制这些事件,需要进一步研究未结合的 α5 是否可以通过一种称为整合素介导的死亡的 caspase 8 依赖性方式主动引发细胞凋亡。

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