Abstract
During 'emergency' situations such as infections, host defense requires rapid mobilization of bone marrow granulocyte progenitors. 'Steady-state' granulopoiesis is absolutely dependent on the C/EBPalpha transcription factor, but the transcriptional mechanisms underlying emergency granulopoiesis remain unclear. Here we show that large numbers of granulocytes were generated from C/EBPalpha-deficient progenitors after cytokine stimulation in vivo. Cytokine treatment or fungal infection induced upregulation of C/EBPbeta but not C/EBPalpha or C/EBPepsilon transcripts in granulocyte progenitors, and C/EBPbeta-deficient progenitors showed decreased emergency-induced granulopoiesis in vitro and in vivo. C/EBPbeta inhibited proliferation less severely than did C/EBPalpha. These data suggest a critical function for C/EBPbeta in emergency granulopoiesis, which demands both differentiation and proliferation of granulocyte precursors.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Animals, Congenic
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CCAAT-Enhancer-Binding Protein-alpha / deficiency
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CCAAT-Enhancer-Binding Protein-alpha / physiology
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CCAAT-Enhancer-Binding Protein-beta / deficiency
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CCAAT-Enhancer-Binding Protein-beta / genetics
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CCAAT-Enhancer-Binding Protein-beta / physiology*
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CCAAT-Enhancer-Binding Proteins / physiology
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Candidiasis / immunology
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Candidiasis / physiopathology
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Cell Cycle
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Cell Differentiation
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Cells, Cultured / metabolism
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Colony-Forming Units Assay
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Estradiol / pharmacology
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Granulocyte Colony-Stimulating Factor / genetics
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Granulocyte Colony-Stimulating Factor / physiology
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics
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Granulocyte-Macrophage Colony-Stimulating Factor / physiology
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Granulocytes / cytology*
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Hematopoiesis / genetics
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Hematopoiesis / physiology*
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Hematopoietic Stem Cells / cytology*
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Hematopoietic Stem Cells / drug effects
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Humans
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Infections / immunology*
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Interleukin-3 / genetics
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Interleukin-3 / physiology
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K562 Cells / cytology
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Mice
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Mice, Inbred C57BL
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Radiation Chimera
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Receptors, Estrogen / drug effects
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Receptors, Estrogen / genetics
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Recombinant Fusion Proteins / physiology
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Transduction, Genetic
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Up-Regulation
Substances
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CCAAT-Enhancer-Binding Protein-alpha
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CCAAT-Enhancer-Binding Protein-beta
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CCAAT-Enhancer-Binding Proteins
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Cebpe protein, mouse
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Interleukin-3
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Receptors, Estrogen
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Recombinant Fusion Proteins
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Granulocyte Colony-Stimulating Factor
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Estradiol
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Granulocyte-Macrophage Colony-Stimulating Factor