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Impaired response to GM-CSF and G-CSF, and enhanced apoptosis in C/EBPbeta-deficient hematopoietic cells.

AbstractTranscription 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.
AuthorsTadayuki Akagi, Takayuki Saitoh, James O'Kelly, Shizuo Akira, Adrian F Gombart, H Phillip Koeffler (Affiliation: Division of Hematology and Oncology, Cedars-Sinai Medical Center, University of California Los Angeles School of Medicine, Los Angeles, CA 90048, USA. akagit at cshs.org)
JournalBlood (Blood) Vol. 111 Issue 6 Pg. 2999-3004 (Mar 15 2008) ISSN: 0006-4971 United States
PMID18056834 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Surface
  • CCAAT-Enhancer-Binding Protein-beta
  • Cytokines
  • RNA, Messenger
  • Granulocyte Colony-Stimulating Factor
  • Fluorouracil
  • Granulocyte-Macrophage Colony-Stimulating Factor
Topics
  • Animals
  • Antigens, Surface (immunology)
  • Apoptosis (drug effects)
  • Bone Marrow Cells (cytology, immunology, metabolism)
  • CCAAT-Enhancer-Binding Protein-beta (deficiency, genetics, metabolism)
  • Cell Lineage
  • Cytokines (genetics)
  • Fluorouracil (pharmacology)
  • Gene Expression Regulation
  • Granulocyte Colony-Stimulating Factor (pharmacology)
  • Granulocyte-Macrophage Colony-Stimulating Factor (pharmacology)
  • Hematopoiesis (drug effects)
  • Leukocytes (cytology, immunology)
  • Mice
  • Mice, Knockout
  • RNA, Messenger (genetics)