Impaired response to GM-CSF and G-CSF, and enhanced apoptosis in C/EBPβ-deficient hematopoietic cells
Impaired response to GM-CSF and G-CSF, and enhanced apoptosis in C/EBPβ-deficient hematopoietic cells
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DOI：
10.1182/blood-2007-04-087213
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发表时间：
2008-03-15
期刊：
影响因子：
20.3
通讯作者：
Koeffler, H. Phillip
中科院分区：
文献类型：
--
作者：
Akagi, Tadayuki;Saitoh, Takayuki;Koeffler, H. Phillip
称为CCAAT增强子结合蛋白（C/EBP）的转录因子参与造血分化，包括骨髓和粒细胞减少。C/EBP β缺陷小鼠发育正常;然而，它们表现出检测巨噬细胞功能，导致对感染的易感性增加。关于G/EBP β在粒细胞生成中的作用知之甚少，因此，我们研究了C/EBP β缺陷小鼠的粒细胞生成。C/EBP β缺陷小鼠的形态、外周血和骨髓细胞数量以及骨髓谱系特异性基因的表达均正常。有趣的是，C/EBP β缺陷小鼠的造血祖细胞对粒细胞/巨噬细胞集落刺激因子和粒细胞集落刺激因子没有正常反应。此外，与野生型中性粒细胞相比，C/EBP β缺陷型中性粒细胞显示出增强的凋亡。我们目前的研究结果表明，C/EBP β有助于调节中性粒细胞的生存，下游的粒细胞集落刺激因子受体。
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.