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骨髓对静脉内移植造血细胞识别的分子基础

Molecular basis of the recognition of intravenously transplanted hemopoietic cells by bone marrow.

作者信息

Aizawa S, Tavassoli M

机构信息

Veterans Administration Medical Center, Jackson, MS.

出版信息

Proc Natl Acad Sci U S A. 1988 May;85(9):3180-3. doi: 10.1073/pnas.85.9.3180.

Abstract

Bone marrow transplantation is done by introducing a source of hemopoietic stem cells into general circulation in anticipation of their recognition and selective lodging into the bone marrow. We tested the hypothesis that the molecular basis of this recognition is by means of a lectin-carbohydrate interaction. We synthesized a number of neoglycoproteins by covalently binding pyranose derivatives of various monosaccharides to bovine serum albumin (BSA). These reagents and the galactosyl-terminating glycoprotein asialofetuin were used to inhibit engraftment of intravenously transplanted marrow cells into lethally irradiated mice. In splenectomized mice, in whom engraftment occurs only in the bone marrow, galactosyl-BSA, mannosyl-BSA, and asialofetuin but not fucosyl-BSA inhibited homing of transplanted cells. Both the survival and cellular content of marrow, including hemopoietic stem cells and granulocyte-macrophage progenitors, were reduced. In nonsplenectomized mice, in whom engraftment occurs in both spleen and marrow, the reagents did not inhibit splenic homing. Both the survival and cellular content of spleen, including hemopoietic stem cells and granulocyte-macrophage progenitors, were similar to those of the control group. But even in this group, marrow homing of transplanted cells was inhibited by these reagents. We conclude that the recognition and homing of intravenously transplanted hemopoietic cells by marrow, but not by spleen, occurs by means of a recognition system with galactosyl and mannosyl specificities.

摘要

骨髓移植是通过将造血干细胞来源引入体循环,以期它们能被识别并选择性地在骨髓中着床来完成的。我们检验了这样一个假说,即这种识别的分子基础是通过凝集素 - 碳水化合物相互作用。我们通过将各种单糖的吡喃糖衍生物共价结合到牛血清白蛋白(BSA)上,合成了多种新糖蛋白。这些试剂以及半乳糖基末端糖蛋白去唾液酸胎球蛋白被用于抑制静脉内移植的骨髓细胞在致死性照射小鼠体内的植入。在脾切除的小鼠中,植入仅发生在骨髓,半乳糖基 - BSA、甘露糖基 - BSA和去唾液酸胎球蛋白可抑制移植细胞归巢,但岩藻糖基 - BSA则不能。骨髓的存活和细胞含量,包括造血干细胞和粒细胞 - 巨噬细胞祖细胞,均减少。在未进行脾切除的小鼠中,植入发生在脾脏和骨髓,这些试剂不抑制脾归巢。脾脏的存活和细胞含量,包括造血干细胞和粒细胞 - 巨噬细胞祖细胞,与对照组相似。但即使在该组中,这些试剂也能抑制移植细胞的骨髓归巢。我们得出结论,骨髓而非脾脏对静脉内移植的造血细胞的识别和归巢,是通过具有半乳糖基和甘露糖基特异性的识别系统实现的。

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