Transforming growth factor beta selectively inhibits normal and leukemic human bone marrow cell growth in vitro.
Transforming growth factor beta selectively inhibits normal and leukemic human bone marrow cell growth in vitro.
复制标题
DOI：
10.1182/blood.v72.5.1504.bloodjournal7251504
复制
发表时间：
1988-11
期刊：
影响因子：
20.3
通讯作者：
G. Sing;J. Keller;L. Ellingsworth;F. Ruscetti
中科院分区：
文献类型：
--
作者：
G. Sing;J. Keller;L. Ellingsworth;F. Ruscetti
本文研究了转化生长因子β_1或β_2（TGF-β_1或β_2）对正常和恶性造血细胞体外增殖和分化的影响。两种形式的TGF-β抑制正常细胞增殖和重组人白细胞介素-3（IL-3）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）诱导的集落形成。在存在GM-CSF或IL-3的情况下，最佳浓度的TGF-β（400 pmol/L）抑制红系（BFU-E）、多能（CFU-GEMM）和粒细胞-巨噬细胞（CFU-GM）祖细胞的集落形成90%至100%，而粒细胞或单核细胞簇形成不受抑制。相反，TGF-β的两种形式对G-CSF诱导的造血都没有任何影响。抑制作用似乎直接由TGF-β介导，因为在辅助细胞耗尽的骨髓细胞中也观察到抗增殖反应。与正常骨髓细胞相比，GM和G-CSF诱导的慢性髓性白血病患者细胞增殖均被TGF-β以剂量依赖性方式抑制。还观察到TGF-β对已建立的白血病细胞系增殖的不同影响，因为所研究的大多数骨髓单核细胞性质的细胞系被强烈抑制，而红系细胞系对TGF-β不敏感或抑制较差。这些结果表明，TGF-β是人造血的重要调节剂，其选择性地调节具有高增殖能力的较不成熟的造血细胞群体的生长，而不是不受TGF-β影响的更分化的细胞。
The effects of transforming growth factor beta 1 or beta 2 (TGF-beta 1 or -beta 2) on the in vitro proliferation and differentiation of normal and malignant human hematopoietic cells were studied. Both forms of TGF-beta suppressed both the normal cellular proliferation and colony formation induced by recombinant human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the presence of GM-CSF or IL-3, optimal concentrations of TGF-beta (400 pmol/L) inhibited colony formation by erythroid (BFU-E), multipotential (CFU-GEMM), and granulocyte-macrophage (CFU-GM) progenitor cells by 90% to 100%, whereas granulocyte or monocyte cluster formation was not inhibited. In contrast, neither form of TGF-beta had any effect on G-CSF-induced hematopoiesis. The suppressive action appeared to be mediated directly by TGF-beta since antiproliferative responses were also observed in accessory cell-depleted bone marrow cells. In contrast to normal bone marrow cells, both GM- and G-CSF-induced proliferation of cells from patients with chronic myelogenous leukemia were suppressed in a dose-dependent manner by TGF-beta. Differential effects of TGF-beta on the proliferation of established leukemic lines were also observed since most cell lines of myelomonocytic nature studied were strongly inhibited where erythroid cell lines were either insensitive or poorly inhibited by TGF-beta. These results suggest that TGF-beta is an important modulator of human hematopoiesis that selectively regulates the growth of less mature hematopoietic cell populations with a high proliferative capacity as opposed to more differentiated cells, which are not affected by TGF-beta.