TY - JOUR
T1 - The granulocyte colony-stimulating factor receptor is required for the mobilization of murine hematopoietic progenitors into peripheral blood by cyclophosphamide or interleukin-8 but not Flt-3 ligand
AU - Liu, Fulu
AU - Poursine-Laurent, Jennifer
AU - Link, Daniel C.
PY - 1997/10/1
Y1 - 1997/10/1
N2 - Hematopoietic progenitor cells (HPC) can be mobilized from the bone marrow into the peripheral circulation in response to a number of stimuli including hematopoietic growth factors, cytotoxic agents, and certain chemokines. Despite significant differences in their biological activities, these stimuli result in the mobilization of HPC with a similar phenotype, suggesting that a common mechanism for mobilization may exist. In this study, the role of granulocyte colony-stimulating factor (G-CSF) in progenitor mobilization was examined using G-CSF receptor (G-CSFR)-deficient mice. In contrast to wild-type mice, no increase in circulating colony-forming cells (CFU-C), CD34+ lineage- progenitors, or day 12 colony-forming unit-spleen progenitors (CFU-S) was detected in G-CSFR-deficient mice after cyclophosphamide administration. This defect was not due to a failure to regenerate HPC following cyclophosphamide administration as the number of CFU-C in the bone marrow of G-CSFR-deficient mice was increased relative to wild-type mice. Likewise, no increase in circulating CFU-C was detested in G- CSFR-deficient mice following interleukin-8 (IL-8) administration. In contrast, mobilization of HPC in response to fit-3 ligand was nearly normal. These results show that the G-CSFR is required for mobilization in response to cyclophosphamide or IL-8 but not fit-3 ligand and suggest that the G-CSFR may play an important and previously unexpected role in HPC migration.
AB - Hematopoietic progenitor cells (HPC) can be mobilized from the bone marrow into the peripheral circulation in response to a number of stimuli including hematopoietic growth factors, cytotoxic agents, and certain chemokines. Despite significant differences in their biological activities, these stimuli result in the mobilization of HPC with a similar phenotype, suggesting that a common mechanism for mobilization may exist. In this study, the role of granulocyte colony-stimulating factor (G-CSF) in progenitor mobilization was examined using G-CSF receptor (G-CSFR)-deficient mice. In contrast to wild-type mice, no increase in circulating colony-forming cells (CFU-C), CD34+ lineage- progenitors, or day 12 colony-forming unit-spleen progenitors (CFU-S) was detected in G-CSFR-deficient mice after cyclophosphamide administration. This defect was not due to a failure to regenerate HPC following cyclophosphamide administration as the number of CFU-C in the bone marrow of G-CSFR-deficient mice was increased relative to wild-type mice. Likewise, no increase in circulating CFU-C was detested in G- CSFR-deficient mice following interleukin-8 (IL-8) administration. In contrast, mobilization of HPC in response to fit-3 ligand was nearly normal. These results show that the G-CSFR is required for mobilization in response to cyclophosphamide or IL-8 but not fit-3 ligand and suggest that the G-CSFR may play an important and previously unexpected role in HPC migration.
UR - http://www.scopus.com/inward/record.url?scp=0030799923&partnerID=8YFLogxK
U2 - 10.1182/blood.v90.7.2522
DO - 10.1182/blood.v90.7.2522
M3 - Article
C2 - 9326216
AN - SCOPUS:0030799923
SN - 0006-4971
VL - 90
SP - 2522
EP - 2528
JO - Blood
JF - Blood
IS - 7
ER -