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Mobilization of CD34 + haematopoietic stem cells is associated with a functional inactivation of the integrin very late antigen 4
Author(s) -
Lichterfeld Mathias,
Martin Simona,
Burkly Linda,
Haas Rainer,
Kronenwett Ralf
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.02130.x
Subject(s) - cd34 , haematopoiesis , homing (biology) , stem cell , bone marrow , biology , stem cell factor , antigen , microbiology and biotechnology , chemistry , immunology , ecology
The β1 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 Mg 2+ 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.