TY - JOUR
T1 - A role for G-CSF receptor signaling in the regulation of hematopoietic cell function but not lineage commitment or differentiation
AU - Semerad, Craig L.
AU - Poursine-Laurent, Jennifer
AU - Liu, Fulu
AU - Link, Daniel C.
N1 - Funding Information:
The authors thank Tomoko Betsuyaku, M. Susan Mudd, J. Michael Shipley, and Robert M. Senior (Washington University) for their expert technical assistance in assessing chemotaxis and MMP-9 expression. We also thank Morgan McLemore (Washington University) for his expert technical assistance and helpful discussions. This work was supported by the Edward Mallinckrodt, Jr., Foundation (D. C. L.), by a grant from Monsanto/Searle (D. C. L.), and by a training grant from the National Institutes of Health National Heart, Lung, and Blood Institute (T 32 HL 07088-23; C. L. S.).
PY - 1999/8
Y1 - 1999/8
N2 - To investigate the specificity of cytokine signals in hematopoietic differentiation, we generated mice with a targeted mutation of their G-CSF receptor (G-CSFR) such that the cytoplasmic (signaling) domain of the G-CSFR is replaced with the cytoplasmic domain of the erythropoietin receptor. In homozygous mutant mice, expression of this chimeric receptor had no apparent affect on lineage commitment and was able to support the production of morphologically mature neutrophils. However, mutant neutrophils displayed reduced chemotaxis, and G-CSF-stimulated mobilization of neutrophils and hematopoietic progenitors from the bone marrow to blood was markedly impaired. Thus, the G-CSFR is generating unique signals that are required for certain specialized hematopoietic cell functions but are not required for granulocytic differentiation or lineage commitment.
AB - To investigate the specificity of cytokine signals in hematopoietic differentiation, we generated mice with a targeted mutation of their G-CSF receptor (G-CSFR) such that the cytoplasmic (signaling) domain of the G-CSFR is replaced with the cytoplasmic domain of the erythropoietin receptor. In homozygous mutant mice, expression of this chimeric receptor had no apparent affect on lineage commitment and was able to support the production of morphologically mature neutrophils. However, mutant neutrophils displayed reduced chemotaxis, and G-CSF-stimulated mobilization of neutrophils and hematopoietic progenitors from the bone marrow to blood was markedly impaired. Thus, the G-CSFR is generating unique signals that are required for certain specialized hematopoietic cell functions but are not required for granulocytic differentiation or lineage commitment.
UR - http://www.scopus.com/inward/record.url?scp=0033180176&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(00)80090-4
DO - 10.1016/S1074-7613(00)80090-4
M3 - Article
C2 - 10485650
AN - SCOPUS:0033180176
VL - 11
SP - 153
EP - 161
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 2
ER -