Keller S, Rupp C, Stoeck A, Runz S, Fogel M, Lugert S, Hager H-D, Abdel-Bakky M S, Gutwein P, Altevogt P
Tumor Immunology Programme, German Cancer Research Center, Heidelberg, Germany.
Kidney Int. 2007 Nov;72(9):1095-102. doi: 10.1038/sj.ki.5002486. Epub 2007 Aug 15.
Exosomes are small membrane vesicles that are secreted from a variety of cell types into various body fluids including the blood and urine. These vesicles are thought to play a role in cell-cell interactions. CD24 is a small but extensively glycosylated protein linked to the cell surface by means of a glycosyl-phosphatidylinositol anchor. In this study we found that CD24 is present in membrane vesicles characterized as exosomes that were isolated from the urine of normal individuals. CD24 was expressed by both tubule cells and podocytes and treatment of the latter with a cholesterol-extracting agent, but not with a calcium ionophore, caused the release of CD24-containing exosomes. Using CD24 as a marker, we found exosomes in the urine of newborn infants and in the amniotic fluid of pregnant women with similar findings made in mice. Interestingly, studies with CD24 knockout mice showed that the exosomes are released from the fetus but not from the mother; however, exosome release was similar from both the knockout and the wild-type mice. This indicates that CD24 is not essential for exosome formation or release but may be a convenient exosome marker. Our studies suggest that exosomal secretion from the embryonic kidney could play a biological role at the fetal-maternal interphase.
外泌体是一种小的膜泡,由多种细胞类型分泌到包括血液和尿液在内的各种体液中。这些小泡被认为在细胞间相互作用中发挥作用。CD24是一种小的但高度糖基化的蛋白质,通过糖基磷脂酰肌醇锚定连接到细胞表面。在本研究中,我们发现CD24存在于从正常个体尿液中分离出的被鉴定为外泌体的膜泡中。CD24在肾小管细胞和足细胞中均有表达,用胆固醇提取剂而非钙离子载体处理足细胞会导致含CD24的外泌体释放。以CD24作为标志物,我们在新生儿尿液和孕妇羊水中发现了外泌体,在小鼠中也有类似发现。有趣的是,对CD24基因敲除小鼠的研究表明,外泌体是从胎儿而非母体释放的;然而,基因敲除小鼠和野生型小鼠的外泌体释放情况相似。这表明CD24对外泌体的形成或释放并非必不可少,但可能是一种方便的外泌体标志物。我们的研究表明,胚胎肾的外泌体分泌可能在胎儿 - 母体界面发挥生物学作用。