Differential role for very late antigen-5 in mobilization and homing of hematopoietic stem cells.
The role of very late antigen-5 (VLA-5) in homing and mobilization of hematopoietic stem cells from normal bone marrow (NBM) and bone marrow (MBM) and peripheral blood (MPB) from mobilized mice was investigated. We found a decreased number of VLA-5-expressing cells in the lineage-negative fraction of MPB. However, virtually all stem/progenitor cells were present in the VLA-5(+) fraction and hence mobilization of hematopoietic stem cell subsets does not coincide with a downregulation of VLA-5. Stem/progenitor cells from MPB and MBM demonstrated enhanced stromal-derived factor-alpha-induced migration. This enhanced migration correlates with an improved hematopoietic reconstitution potential, with the migrated MPB cells showing the fastest reconstitution. Interestingly, homing of MPB, MBM and NBM stem/progenitor cells in bone marrow and spleen did not differ and is therefore not responsible for the differences in hematopoietic reconstitution. The observed increase in VLA-5(+) cells in the recipients after transplantation can most probably be attributed to selective homing of VLA-5(+) cells instead of an upregulation of VLA-5. Treatment with an antibody to VLA-5 partially inhibited bone marrow homing of progenitor cells, whereas homing in the spleen was hardly affected. These data indicate a differential role for VLA-5 in the movement of stem cells from and toward bone marrow.
Wierenga
P K
PK
Department of Cell Biology, Section of Stem Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. p.k.wierenga@med.umcg.nl
Weersing
E
E
Dontje
B
B
de Haan
G
G
van Os
R
R
D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D006410:Hematopoiesis / Q000502:physiology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D051379:Mice; D013154:Spleen / Q000166:cytology / Q000502:physiology
D039081:Integrin alpha5beta1