RRC ID 39484
Author Takagi M, Nakamura T, Sawada T, Kaneko A, Nozaki-Ukai M, Nakahata T, Yokota T, Heike T.
Title Chimeric cytokine receptor can transduce expansion signals in interleukin 6 receptor alpha (IL-6Ralpha)-, IL-11Ralpha-, and gp130-low to -negative primitive hematopoietic progenitors.
Journal Mol. Biol. Cell
Abstract We generated transgenic mice expressing chimeric receptors, which comprise extracellular domains of the human granulocyte-macrophage colony-stimulating factor (hGM-CSF) receptor and transmembrane and cytoplasmic domains of the mouse leukemia inhibitory factor receptor. In suspension cultures of lineage-negative (Lin(-)), 5-fluorouracil-resistant bone marrow cells of the transgenic mice, a combination of hGM-CSF and stem cell factor (SCF) induced exponential expansions of mixed colony-forming unit. The combination of hGM-CSF and SCF was effective on enriched, Lin(-)Sca-1(+)c-kit(+) progenitors and increased either mixed colony-forming unit or cobblestone area-forming cells. In case of stimulation with hGM-CSF and SCF, interleukin-6 (IL-6) and SCF, or IL-11 and SCF, the most efficient expansion was achieved with hGM-CSF and SCF. When Lin(-)Sca-1(+)c-kit(+)CD34(-) further enriched progenitors were clone sorted and individually incubated in the presence of SCF, hGM-CSF stimulated a larger number of cells than did IL-6, IL-6 and soluble IL-6 receptor (IL-6R), or IL-11. These data suggest the presence of IL-6Ralpha-, IL-11Ralpha-, and gp130-low to -negative primitive hematopoietic progenitors. Such primitive progenitors are equipped with signal transduction molecules and can expand when these chimeric receptors are genetically introduced into the cells and stimulated with hGM-CSF in the presence of SCF.
Volume 10(11)
Pages 3633-42
Published 1999-11
DOI 10.1091/mbc.10.11.3633
PMID 10564261
PMC PMC25652
MeSH Animals Antigens, CD / metabolism* Clone Cells Colony-Forming Units Assay Cytokine Receptor gp130 Flow Cytometry Fluorouracil / pharmacology Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology Growth Inhibitors* Hematopoietic Stem Cells / metabolism* Humans Interleukin-11 Receptor alpha Subunit Interleukin-6* Leukemia Inhibitory Factor Leukemia Inhibitory Factor Receptor alpha Subunit Lymphokines* Membrane Glycoproteins / metabolism* Mice Mice, Transgenic Receptors, Cytokine / genetics Receptors, Cytokine / metabolism* Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics Receptors, Interleukin / metabolism* Receptors, Interleukin-11 Receptors, Interleukin-6 / metabolism* Receptors, OSM-LIF Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism
IF 3.512
Times Cited 4
Human and Animal Cells