C/EBPbeta is required for 'emergency' granulopoiesis.
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.
Hirai
Hideyo
H
Harvard Institutes of Medicine and Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA.
Zhang
Pu
P
Dayaram
Tajhal
T
Hetherington
Christopher J
CJ
Mizuno
Shin-ichi
S
Imanishi
Jiro
J
Akashi
Koichi
K
Tenen
Daniel G
DG
D000818:Animals; D020296:Animals, Congenic; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000172:deficiency / Q000502:physiology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology; D002177:Candidiasis / Q000276:immunology / Q000503:physiopathology; D002453:Cell Cycle; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000378:metabolism; D003114:Colony-Forming Units Assay; D004958:Estradiol / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology; D006098:Granulocytes / Q000166:cytology*; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007239:Infections / Q000276:immunology*; D007377:Interleukin-3 / Q000235:genetics / Q000502:physiology; D020014:K562 Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014161:Transduction, Genetic; D015854:Up-Regulation
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C489468:Cebpe protein, mouse; D007377:Interleukin-3; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D016179:Granulocyte Colony-Stimulating Factor; D004958:Estradiol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor