Coexpression in humans by kidney and fetal envelopes of a 280 kDa-coated pit-restricted protein. Similarity with the murine target of teratogenic antibodies.
Coexpression in humans by kidney and fetal envelopes of a 280 kDa-coated pit-restricted protein. Similarity with the murine target of teratogenic antibodies.
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人类肾脏和胎儿包膜共表达 280 kDa 包被的凹坑限制蛋白。
DOI：
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发表时间：
1992
影响因子：
6
通讯作者：
P. Verroust
中科院分区：
文献类型：
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作者：
D. Sahali;N. Mulliez;F. Châtelet;C. Laurent‐Winter;D. Citadelle;C. Roux;Pierre M. Ronco;P. Verroust
过去三十年来在大鼠中进行的实验研究表明，针对肾脏或卵黄囊（在大鼠中，肾脏或卵黄囊围绕胚胎并在妊娠的主要阶段充当胎盘）产生的抗体会诱导胎儿吸收或畸形。一般认为，致畸性抗体减少卵黄囊上皮细胞对母体蛋白的内化和降解，导致胚胎营养供应不足。这些观察结果表明，抗体对胎儿包膜的致病作用在临床病理学中具有很大的潜在意义，因为大多数人类胎儿畸形病例的原因不明。作者最近表明，小鼠系统中的关键致畸性抗体针对280 kDa包被的pit蛋白（gp280），该蛋白对肾近端小管和卵黄囊上皮细胞的刷状缘具有特异性。这一观察为在人类中寻找类似系统提供了独特的机会。在这项研究中，在人类中存在的蛋白质密切相关的小鼠gp280显示，广泛的免疫交叉反应性，密切的表观分子量，强同源性的二维肽图，并在器官和亚细胞水平的限制性分布。除肾脏和卵黄囊外，在胎盘合胞体滋养层细胞的包被陷窝内也检测到人gp280。当引入体外大鼠胚胎培养系统时，人gp280抗体以剂量依赖性方式诱导发育异常。这些观察结果表明，小鼠模型的抗原组分存在于人类中，并可产生引起发育异常的异源抗体，表明该实验模型可能在人类病理学中具有重要意义。
Experimental studies performed in the rat over the last three decades have shown that antibodies raised against kidney or yolk sac, which, in the rat, surrounds the embryo and serves as a placenta during the major part of pregnancy, induced fetal resorptions or malformations. It is generally considered that the teratogenic antibodies decrease internalization and degradation of maternal proteins by yolk sac epithelial cells leading to an inadequate supply of nutriments to the embryo. These observations demonstrating the pathogenic role of antibodies to fetal envelopes are of great potential interest in clinical pathology since most cases of fetal malformations in humans are of unknown cause. The authors have recently shown that the key teratogenic antibodies in the murine system were directed against a 280 kDa-coated pit protein (gp280) specific for the brush border of epithelial cells lining the renal proximal tubule and the yolk sac. This observation allows for the unique opportunity to search for a similar system in humans. In this study, the presence in humans of a protein closely related to murine gp280 is shown, as indicated by extensive immunologic crossreactivity, close apparent molecular weights, strong homology of bidimensional peptide maps, and restricted distribution at the organ and subcellular level. In addition to kidney and yolk sac, human gp280 was also detected within the coated pits of the placental syncytiotrophoblastic cells. When introduced in an in vitro rat embryo culture system, antibodies to human gp280-induced developmental anomalies in a dose-dependent manner. These observations indicate that the antigenic component of the murine model is present in humans and can give rise to heterologous antibodies that cause developmental anomalies, suggesting that the experimental model might be of significance in human pathology.