Impaired response to GM-CSF and G-CSF, and enhanced apoptosis in C/EBPbeta-deficient hematopoietic cells.
Transcription factors known as CCAAT enhancer binding proteins (C/EBPs) are involved in hematopoietic differentiation, including myelopoiesis and granulopoiesis. C/EBPbeta-deficient mice develop normally; however, they exhibit defective macrophage function, resulting in increased susceptibility to infection. Little is known about the role of C/EBPbeta in granulopoiesis; therefore, we examined granulopoiesis in C/EBPbeta-deficient mice. Morphology, the number of peripheral blood and bone marrow cells, and the expression of genes specific for the myeloid lineage were normal in C/EBPbeta-deficient mice. Interestingly, the hematopoietic progenitor cells of C/EBPbeta-deficient mice did not respond normally to granulocyte/macrophage-colony stimulating factor and granulocyte colony stimulating factor. In addition, C/EBPbeta-deficient neutrophils displayed enhanced apoptosis compared with wild-type neutrophils. Our present results indicate that C/EBPbeta helps regulate survival of neutrophils, downstream of the granulocyte colony stimulating factor receptor.
Akagi
Tadayuki
T
Division of Hematology and Oncology, Cedars-Sinai Medical Center, University of California Los Angeles School of Medicine, Los Angeles, CA 90048, USA. akagit@cshs.org
Saitoh
Takayuki
T
O'Kelly
James
J
Akira
Shizuo
S
Gombart
Adrian F
AF
Koeffler
H Phillip
HP
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D016207:Cytokines / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics
D000954:Antigens, Surface; D022782:CCAAT-Enhancer-Binding Protein-beta; D016207:Cytokines; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005472:Fluorouracil