Hoang T, Levy B, Onetto N, Haman A, Rodriguez-Cimadevilla J C
Clinical Research Institute of Montreal, Quebec, Canada.
J Exp Med. 1989 Jul 1;170(1):15-26. doi: 10.1084/jem.170.1.15.
TNF-alpha has been shown to antagonize the proliferative effects of growth factors present in crude conditioned media from PHA-stimulated leukocytes or cell lines on the clonogenic cells of acute myeloblastic leukemia (AML) (19,21). In the present study, we investigated the responses of AML blasts to TNF-alpha in the presence of defined growth factors (recombinant granulocyte/macrophage-CSF [rGM-CSF], recombinant granulocyte-CSF [rG-CSF], rIL-3, and rIL-1) and under conditions described for autocrine stimulation (32). While TNF-alpha antagonized the stimulatory effects of G-CSF and IL-3 on blast progenitors, TNF-alpha did not affect blast colony formation in the presence of IL-1. Unexpectedly, TNF-alpha significantly enhanced blast proliferation in the presence of GM-CSF. Further, TNF-alpha also acted synergistically with an endogenous source of growth stimulatory signal to promote proliferation of blast clonogenic cells. Thus, on human leukemic cells, TNF-alpha appears to be a molecule that is at least bifunctional, having the ability to either support or inhibit cell proliferation, depending on the other growth factors present. It is postulated that the proliferative response of blast progenitors to TNF-alpha under conditions that favor autocrine stimulation may represent one property that allows the cells to escape from negative regulation and proliferate in AML.
肿瘤坏死因子-α（TNF-α）已被证明可拮抗PHA刺激的白细胞或细胞系的粗制条件培养基中存在的生长因子对急性髓性白血病（AML）克隆形成细胞的增殖作用（19,21）。在本研究中，我们研究了在特定生长因子（重组粒细胞/巨噬细胞集落刺激因子[rGM-CSF]、重组粒细胞集落刺激因子[rG-CSF]、rIL-3和rIL-1）存在的情况下以及在自分泌刺激所描述的条件下（32），AML原始细胞对TNF-α的反应。虽然TNF-α拮抗了G-CSF和IL-3对原始祖细胞的刺激作用，但在IL-1存在的情况下，TNF-α并不影响原始细胞集落形成。出乎意料的是，在GM-CSF存在的情况下，TNF-α显著增强了原始细胞的增殖。此外，TNF-α还与内源性生长刺激信号协同作用，促进原始克隆形成细胞的增殖。因此，在人类白血病细胞上，TNF-α似乎是一种至少具有双功能的分子，根据存在的其他生长因子的情况，它具有支持或抑制细胞增殖的能力。据推测，在有利于自分泌刺激的条件下，原始祖细胞对TNF-α的增殖反应可能代表了一种使细胞能够逃避负调控并在AML中增殖的特性。
