ROLE OF THE 75-KDA TUMOR-NECROSIS-FACTOR RECEPTOR - INHIBITION OF EARLY HEMATOPOIESIS
ROLE OF THE 75-KDA TUMOR-NECROSIS-FACTOR RECEPTOR - INHIBITION OF EARLY HEMATOPOIESIS
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DOI：
10.1073/pnas.91.22.10695
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发表时间：
1994-10-25
影响因子：
11.1
通讯作者：
JACOBSEN, SEW
中科院分区：
文献类型：
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作者：
JACOBSEN, FW;ROTHE, M;JACOBSEN, SEW
肿瘤坏死因子 cu (TNF-α) 的生物学效应是通过两种细胞表面受体介导的，即 55-kDa TNF 受体和 75-kDa TNF 受体。本研究调查了两种 TNF 受体在正常造血过程中的相对作用。使用 55-kDa 和 75-kDa TNF 受体特异性激动剂（抗体），我们证明了两种 TNF 受体在造血中的不同作用，因为只有 55-kDa TNF 受体介导 TNF-α 对响应粒细胞集落刺激因子的成熟 Lin(-) 造血祖细胞的抗增殖作用 或单独的白细胞介素3。相反，75-kDa TNF 受体对于介导原始 Lin(-)Sca-1(+) 高增殖潜能集落形成细胞的抑制以及对单独培养的 Lin(-)Sca-1(+)Rh123(lo) 和 Lin-Sca-1(+)Rh123(hi) 细胞的增殖克隆总数的抑制至关重要。
Biological effects of tumor necrosis factor cu (TNF-alpha) are mediated through two cell surface receptors, the 55-kDa TNF receptor and the 75-kDa TNF receptor. The present study investigated the relative roles of the two TNF receptors in normal hematopoiesis. Using agonists (antibodies) specific for the 55- and 75-kDa TNF receptors, we demonstrate differential roles of the two TNF receptors in hematopoiesis in that only the 55-kDa TNF receptor mediates antiproliferative effects of TNF-alpha on mature Lin(-) hematopoietic progenitor cells responding to granulocyte colony-stimulating factor or interleukin 3 alone. In contrast, the 75-kDa TNF receptor is essential in mediating inhibition of primitive Lin(-)Sca-1(+) high-proliferative-potential colony-forming cells and inhibition of the total number of proliferative clones of individually cultured Lin(-)Sca-1(+)Rh123(lo) and Lin-Sca-1(+)Rh123(hi) cells.