Different adhesive characteristics and VLA-4 expression of CD34(+) progenitors in G0/G1 versus S+G2/M phases of the cell cycle.
We identified the cell cycle status of CD34(+) cells of steady-state bone marrow (BM) and peripheral blood (PB) obtained from healthy volunteers, and those of apherasis PB samples collected from healthy donors who had been administered granulocyte colony-stimulating factor (G-CSF). More than 10% of CD34(+) cells in BM were in S+G2/M phase. In contrast, regardless of whether G-CSF treatment was performed, less than 2% of CD34(+) cells in PB were cycling. BM CD34(+) cells showed greater VLA-4 expression and adherence to stromal cells than PB CD34(+) cells. In addition, when cycling and dormant BM CD34(+) cells were analyzed separately, the cells in S+G2/M phase expressed more VLA-4 and adhered to the stromal cell monolayer more efficiently than the cells in G0/G1 phase. Furthermore, this adhesion of CD34(+) cells to the stromal cell layer was almost completely inhibited by anti-VLA-4 antibody. Taken together, these results suggest that CD34(+) progenitors in G0/G1 phase of the cell cycle differ from those in S+G2/M phase in adhesiveness mediated by VLA-4 in the hematopoietic microenvironment.
Hokkaido Red Cross Blood Center, Sapporo, Japan.
M
M
Yamaguchi
K
K
Ikebuchi
F
F
Hirayama
N
N
Sato
Y
Y
Mogi
J
J
Ohkawara
Y
Y
Yoshikawa
K
K
Sawada
T
T
Koike
S
S
Sekiguchi
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018952:Antigens, CD34 / Q000032:analysis; D001773:Blood Cells; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D000069585:Filgrastim; D005786:Gene Expression Regulation / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007377:Interleukin-3 / Q000494:pharmacology*; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology*; D017154:Stromal Cells / Q000166:cytology
D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D039041:Integrin alpha4beta1; D016023:Integrins; D007377:Interleukin-3; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim