Submitted April 25, 2007
Accepted November 20, 2007
Impaired response to GM-CSF and G-CSF, and enhanced apoptosis in C/EBP
-deficient hematopoietic cells
Tadayuki Akagi*, Takayuki Saitoh, James O'Kelly, Shizuo Akira, Adrian F Gombart, and H. Phillip Koeffler
Division of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, United States
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
* Corresponding author; email: akagit{at}cshs.org.
Transcription factors known as CCAAT enhancer binding proteins (C/EBPs) are involved in hematopoietic differentiation including myelopoiesis and granulopoiesis. C/EBP
-deficient mice develop normally; however, they exhibit defective macrophage function, resulting in increased susceptibility to infection. Little is known about the role of C/EBP in granulopoiesis; therefore, we examined granulopoiesis in C/EBP-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/EBP-deficient mice. Interestingly, the hematopoietic progenitor cells of C/EBP-deficient mice did not respond normally to GM-CSF and G-CSF. In addition, C/EBP-deficient neutrophils displayed enhanced apoptosis compared with wild-type neutrophils. Our present results indicate that C/EBP helps regulate survival of neutrophils, downstream of the G-CSF receptor.
