Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei City, Anhui Province 230001, China.
Glycobiology. 2013 Oct;23(10):1184-91. doi: 10.1093/glycob/cwt055. Epub 2013 Jul 29.
Selectins and their carbohydrate ligands mediate the homing of hematopoietic stem/progenitor cells (HSPCs) to the bone marrow. We have previously shown that ex vivo fucosylation of selectin ligands on HSPCs by α1,3 fucosyltransferase VI (FUT6) leads to improved human cord blood (CB)-HSPC engraftment in non-obese diabetic (NOD)/severe combined immune deficient (SCID) mice. In the present study, we determined whether surface fucosylation with α1,3 fucosyltransferase VII (FUT7), which is primarily expressed by hematopoietic cells, improves the function of selectin ligands on CB-HSPCs in comparison with FUT6. A saturating amount of either FUT6 or FUT7, which generates comparable levels of expression of fucosylated epitopes on CB CD34(+) cells, was used for these experiments. In vitro, FUT7-treated CB CD34(+) cells exhibited greater binding to P- or E-selectin than that of FUT6-treated CB CD34(+) cells under static or physiological flow conditions. In vivo, FUT7 treatment, like FUT6, improved the early engraftment of CB CD34(+) cells in the bone marrow of sublethally irradiated NOD/SCID interleukin (IL)-2Rγ(null) (NSG) mice. FUT7 also exhibited marginally-yet statistically significant-increased engraftment at 4 and 6 weeks after transplantation. In addition, FUT7-treated CB CD34(+) cells exhibited increased homing to the bone marrow of irradiated NSG mice relative to sham-treated cells. These data indicate that FUT7 is effective at improving the function of selectin ligands on CB-HSPCs in vitro and enhancing early engraftment of treated CB-HSPCs in the bone marrow of recipients.
选择素及其碳水化合物配体介导造血干/祖细胞（HSPCs）归巢到骨髓。我们之前已经表明，通过α1,3 岩藻糖基转移酶 VI（FUT6）对 HSPCs 上的选择素配体进行体外岩藻糖基化可导致改善人脐血（CB）-HSPC 在非肥胖糖尿病（NOD）/严重联合免疫缺陷（SCID）小鼠中的植入。在本研究中，我们确定了主要由造血细胞表达的α1,3 岩藻糖基转移酶 VII（FUT7）的表面岩藻糖基化是否可改善 CB-HSPC 上选择素配体的功能，与 FUT6 相比。使用 FUT6 或 FUT7 的饱和量进行这些实验，该量在 CB CD34(+)细胞上产生可比水平的岩藻糖基化表位表达。在体外，在静态或生理流动条件下，与 FUT6 处理的 CB CD34(+)细胞相比，FUT7 处理的 CB CD34(+)细胞表现出对 P 或 E 选择素的更大结合。在体内，FUT7 处理，如 FUT6，改善了 CB CD34(+)细胞在亚致死照射的 NOD/SCID 白细胞介素（IL）-2Rγ( 空)（NSG）小鼠骨髓中的早期植入。FUT7 还表现出稍高但统计学上显著的在移植后 4 周和 6 周时的植入增加。此外，与 sham 处理的细胞相比，FUT7 处理的 CB CD34(+)细胞表现出向照射的 NSG 小鼠骨髓的归巢增加。这些数据表明，FUT7 可有效改善 CB-HSPC 上选择素配体的功能，并增强处理后的 CB-HSPC 在受者骨髓中的早期植入。
