Mobilization of CD34+ haematopoietic stem cells is associated with a functional inactivation of the integrin very late antigen 4.
The beta1 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.
Klinische Kooperationseinheit Molekulare Hämatologie/Onkologie, Deutsches Krebsforschungszentrum Heidelberg, Germany.
M
M
Lichterfeld
S
S
Martin
L
L
Burkly
R
R
Haas
R
R
Kronenwett
D018952:Antigens, CD34; D002448:Cell Adhesion / Q000502:physiology; D018920:Coculture Techniques; D004727:Endothelium / Q000166:cytology; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D011485:Protein Binding; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D018952:Antigens, CD34; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor; D008274:Magnesium