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CD24和Siglec-10在孕早期胎盘的表达:对胎儿-母体界面免疫耐受的影响

Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface.

作者信息

Sammar Marei, Siwetz Monika, Meiri Hamutal, Fleming Viktor, Altevogt Peter, Huppertz Berthold

机构信息

Prof. Ephraim Katzir Department of Biotechnology Engineering, ORT Braude College, P.O. Box 78, 2161002, Karmiel, Israel.

Institute of Cell Biology, Histology and Embryology, Medical University of Graz, 8010, Graz, Austria.

出版信息

Histochem Cell Biol. 2017 May;147(5):565-574. doi: 10.1007/s00418-016-1531-7. Epub 2016 Dec 23.

Abstract

During pregnancy, the fetal-maternal interface establishes immune tolerance between the fetus and the mother. CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). This interaction was assessed as a candidate complex for the immune suppression response in the placenta. CD24 was affinity purified from term placenta and characterized by SDS-PAGE, Western blot and ELISA. Binding of recombinant Siglecs to placental CD24 was evaluated by ELISA. The expression of CD24 and Siglec-10 in first trimester placental tissues was investigated by immunohistochemistry and immunofluorescence. Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. CD24 did not interact with Siglec-3 or Siglec-5. During the first trimester, and already in gestational week (GA) 8, CD24 showed high expression in villous and extravillous cytotrophoblasts. There was also a mild expression in stromal cells, while syncytiotrophoblasts were negative. Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. The presence of the CD24-Siglec-10 in these regions of fetal-maternal interactions suggests a possible role in mediating immune tolerance at the fetal-maternal interface.

摘要

在孕期,胎儿 - 母体界面建立了胎儿与母亲之间的免疫耐受。CD24是一种在造血细胞和多种肿瘤细胞表面表达的黏蛋白样糖蛋白,已知其可与唾液酸结合免疫球蛋白型凝集素(Siglecs)相互作用。这种相互作用被评估为胎盘免疫抑制反应的候选复合物。从足月胎盘亲和纯化CD24,并通过SDS - PAGE、蛋白质印迹法和酶联免疫吸附测定(ELISA)对其进行表征。通过ELISA评估重组Siglecs与胎盘CD24的结合。通过免疫组织化学和免疫荧光研究了孕早期胎盘组织中CD24和Siglec - 10的表达。胎盘CD24的表观分子量为30 - 70 kDa,与其高度的N - 连接和O - 连接糖基化一致。观察到通过CD24的末端唾液酸聚糖残基存在对乙二胺四乙酸(EDTA)敏感的CD24 - Siglec - 10相互作用。CD24不与Siglec - 3或Siglec - 5相互作用。在孕早期,甚至在妊娠第8周时,CD24在绒毛和绒毛外细胞滋养层中高表达。基质细胞中也有轻度表达,而合体滋养层细胞为阴性。在子宫内膜腺体和与细胞外滋养层紧邻的孕早期蜕膜细胞中观察到CD24与Siglec - 10的共定位。本研究首次证明CD24在胎盘细胞滋养层、胎盘床和母体子宫腺体中早期存在。胎儿 - 母体相互作用的这些区域中CD24 - Siglec - 10的存在表明其在介导胎儿 - 母体界面免疫耐受中可能发挥作用。

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