Jacobsen F W, Rothe M, Rusten L, Goeddel D V, Smeland E B, Veiby O P, Slørdal L, Jacobsen S E
Department of Immunology, Norwegian Radium Hospital, Montebello, Oslo.
Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10695-9. doi: 10.1073/pnas.91.22.10695.
Biological effects of tumor necrosis factor alpha (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+Rh123lo and Lin-Sca-1+Rh123hi cells.
肿瘤坏死因子α(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的TNF受体和75 kDa的TNF受体。本研究调查了这两种TNF受体在正常造血过程中的相对作用。使用针对55 kDa和75 kDa TNF受体的特异性激动剂(抗体),我们证明了这两种TNF受体在造血过程中的不同作用,即只有55 kDa的TNF受体介导TNF-α对单独响应粒细胞集落刺激因子或白细胞介素3的成熟Lin-造血祖细胞的抗增殖作用。相比之下,75 kDa的TNF受体在介导对原始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+Rh123lo和Lin-Sca-1+Rh123hi细胞增殖克隆总数的抑制方面至关重要。