Mobilization of CD34+ haematopoietic stem cells is associated with a functional inactivation of the integrin very late antigen 4

被引:45
作者
Lichterfeld, M
Martin, S
Burkly, L
Haas, R
Kronenwett, R
机构
[1] Univ Dusseldorf, Klin Hamatol Onkol & Klin Immunol, D-40225 Dusseldorf, Germany
[2] Deutsch Krebsforschungszentrum, Klin Kooperationseinheit Mol Hamatol Onkol, D-6900 Heidelberg, Germany
[3] Univ Dusseldorf, Klin Hamatol Onkol & Klin Immunol, Dusseldorf, Germany
[4] Biogen Inc, Cambridge, MA 02142 USA
关键词
VLA-4; affinity states; haematopoietic stem cells; mobilization; cell adhesion;
D O I
10.1046/j.1365-2141.2000.02130.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The beta 1 integrin very late antigen 4 (VLA-4) plays a central role in mobilization and homing of CD34(+) cells. In this study, we examined the activation state of VLA-4 on CD34(+) cells from bone marrow (BM) and peripheral blood (PB) by flow cytometry using a vascular cell adhesion molecule I-immunoglobulin (VCAM-I/IgG) fusion protein as soluble ligand. In an intraindividual analysis, we found a significantly reduced affinity and avidity of the VLA-4 receptor on CD34(+) cells from PB during granulocyte colony-stimulating factor (G-CSF)-enhanced marrow recovery in comparison with steady-state BM. Moreover, the amount of circulating CD34(+) cells during marrow recovery was inversely related to the activation state but not to the expression level of VLA-4, suggesting that a modulation of the functional state of VLA-4 is involved in the mobilization of CD34(+) cells. Moreover, VLA-4 function on CD34(+) cells from BM was associated with the maturation state of CD34(+) cells as high-affinity VLA-4 receptors were observed on the vast majority of more primitive CD34(+) cells. In addition, we found that Mg2+ ions as well as co-incubation of CD34(+) cells with endothelial cells resulted in an activation of the VLA-4 receptor. In conclusion, modulation of the functional state of VLA-4 appears to be of relevance for the mobilization and homing of CD34(+) haematopoietic stem cells.
引用
收藏
页码:71 / 81
页数:11
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