The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34+ cells:: role in transendothelial/stromal migration and engraftment of NOD/SCID mice
The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34+ cells:: role in transendothelial/stromal migration and engraftment of NOD/SCID mice
复制标题
DOI：
10.1182/blood.v95.11.3289.011k33_3289_3296
复制
发表时间：
2000-06-01
期刊：
影响因子：
20.3
通讯作者：
Lapidot, T
中科院分区：
文献类型：
--
作者：
Peled, A;Kollet, O;Lapidot, T
造血干细胞归巢和植入需要几个粘附相互作用，这是不完全理解。非肥胖/严重联合免疫缺陷（NOD/SCID）小鼠移植的人干细胞是依赖于主要的整合素非常晚活化抗原-4（VLA-4）; VLA-5;并在较小程度上，淋巴细胞功能相关抗原-1（LFA-1）。用VLA-4或VLA-5的抗体处理人CD 34（+）细胞阻止了植入，用抗LFA-1抗体处理显著降低了植入水平。用基质衍生因子1（SDF-1）激活携带趋化因子受体CXCR 4的CD 34（+）细胞，导致牢固的粘附和跨内皮迁移，这依赖于LFA-1/ICAM-1（细胞内粘附分子-1）和VLA-4/VCAM-1（血管粘附分子-1）。此外，SDF 1诱导的CD 34（+）/CXCR 4（+）细胞通过内皮细胞外基质的极化和外渗依赖于VLA-4和VLA-5。我们的研究结果表明，重新填充的人干细胞功能表达LFA-1，VLA-4和VLA-5，此外，这项研究意味着一种新的方法，以进一步推进临床移植。（血。2000;95：3289-3296）（C）2000由美国血液学学会。
Hematopoietic stem cell homing and engraftment require several adhesion Interactions, which are not fully understood. Engraftment of nonobese/severe combined immunodeficiency (NOD/SCID) mice by human stem cells is dependent on the major integrins very late activation antigen-4 (VLA-4); VLA-5; and to a lesser degree, lymphocyte function associated antigen-1 (LFA-1). Treatment of human CD34(+) cells with antibodies to either VLA-4 or VLA-5 prevented engraftment, and treatment with anti-LFA-l antibodies significantly reduced the levels of engraftment. Activation of CD34(+) cells, which bear the chemokine receptor CXCR4, with stromal derived factor 1 (SDF-1) led to firm adhesion and transendothelial migration, which was dependent on LFA-1/ICAM-1 (Intracellular adhesion molecule-1)and VLA-4/VCAM-1 (vascular adhesion molecule-1). Furthermore, SDF1-induced polarization and extravasation of CD34(+)/CXCR4(+) cells through the extracellular matrix underlining the endothelium was dependent on both VLA-4 and VLA-5. Our results demonstrate that repopulating human stem cells functionally express LFA-1, VLA-4, and VLA-5, Furthermore, this study implies a novel approach to further advance clinical transplantation.(Blood. 2000;95:3289-3296) (C) 2000 by The American Society of Hematology.