Schumacher U, Mollgård K
University of Southampton, United Kingdom.
Histochem Cell Biol. 1997 Aug;108(2):179-82. doi: 10.1007/s004180050159.
The multidrug-resistance P-glycoprotein (Pgp) was initially identified as an energy-dependent proton pump, which transports a variety of non-related compounds out of chemotherapy-resistant cancer cells. Molecular biological investigations using knockout mice for the mouse homologue of the human Pgp showed that these mice partially lack a functioning blood-brain barrier, indicating that Pgp has an important role in the blood-brain barrier as its normal function. The presence of Pgp expression in formalin-fixed and wax-processed tissue sections can be assessed using the monoclonal antibody, JSB-1. Since no data on the developmental expression of Pgp are available, we stained a developmental series of human brain sections with JSB-1. Our results indicate that Pgp expression in endothelia of brain microvessels occurs regularly in embryos of about 30-mm crown-rump length (CRL). Strong reactivity is seen in blood vessels of fetuses from 123-mm CRL. There is also reactivity in pial blood vessels but not in choroid plexus blood vessels known to be without a blood-brain barrier. Pgp expression is therefore an early marker of the blood-brain barrier in the developing human brain.
多药耐药性P-糖蛋白(Pgp)最初被鉴定为一种能量依赖性质子泵,它将多种不相关的化合物转运出对化疗耐药的癌细胞。使用人Pgp小鼠同源物的基因敲除小鼠进行的分子生物学研究表明,这些小鼠部分缺乏正常功能的血脑屏障,这表明Pgp在血脑屏障中作为其正常功能发挥着重要作用。可以使用单克隆抗体JSB-1评估福尔马林固定和石蜡处理的组织切片中Pgp的表达情况。由于尚无关于Pgp发育表达的数据,我们用JSB-1对一系列发育中的人脑切片进行了染色。我们的结果表明,在约30毫米冠臀长(CRL)的胚胎中,脑微血管内皮细胞中的Pgp表达正常出现。在123毫米CRL的胎儿血管中可见强反应性。软脑膜血管也有反应,但已知没有血脑屏障的脉络丛血管中没有反应。因此,Pgp表达是发育中的人脑血脑屏障的早期标志物。