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

Transcription factors known as CCAAT enhancer binding proteins (C/EBPs) are involved in hematopoietic differentiation, including myelopolesis and granulopolesis. C/EBP beta-deficient mice develop normally; however, they exhibit detective macrophage function, resulting in increased susceptibility to infection. Little is known about the role of G/EBP beta in granulopoiesis; therefore, we examined granulopoiesis in C/EBP beta-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 beta-deficient mice. Interestingly, the hematopoietic progenitor cells of C/EBP beta-deficient mice did not respond normally to granulocyte/macrophage-colony stimulating factor and granulocyte colony stimulating factor. In addition, C/EBP beta-deficient neutrophils displayed enhanced apoptosis compared with wild-type neutrophils. Our present results indicate that C/EBP beta helps regulate survival of neutrophils, downstream of the granulocyte colony stimulating factor receptor.