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

C/EBPbeta 缺乏的造血细胞对 GM-CSF 和 G-CSF 的反应受损,细胞凋亡增强

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作者:Tadayuki Akagi, Takayuki Saitoh, James O'Kelly, Shizuo Akira, Adrian F Gombart, H Phillip Koeffler

Abstract

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.

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