Bradbury D, Bowen G, Kozlowski R, Reilly I, Russell N
University Department of Haematology City Hospital, Nottingham, U.K.
Leukemia. 1990 Jan;4(1):44-7.
We have studied peripheral blood blast cells from a patient with acute myeloblastic leukemia (AML) whose cells proliferated autonomously at high cell density, but only in the presence of adherent cells. At low cell density in suspension culture and in a clonogenic assay, blast cell growth was stimulated by recombinant granulocyte macrophage colony stimulating factor (GM-CSF) and recombinant interleukin-1 (IL-1) independently. The response to rIL-1 was inhibited (less than 90%) by anti-GM-CSF, suggesting that the proliferative response to IL-1 was mediated by GM-CSF. This was supported by experiments which demonstrated that blast cell conditioned medium prepared in the presence of IL-1 contained GM-CSF activity which stimulated the growth of normal granulocyte-macrophage precursors (CFU-GM) and of homologous GM-CSF responsive AML blasts. As IL-1 but no GM-CSF activity was detected in BCCM prepared without exogenous IL-1 and a neutralizing antibody to IL-1 inhibited the autonomous growth of blasts in suspension culture, we conclude that the endogenous secretion of IL-1 by leukemic cells stimulated autocrine GM-CSF secretion, inducing autonomous growth of the blast cell population.
我们研究了一名急性髓细胞白血病（AML）患者的外周血原始细胞，该患者的细胞在高细胞密度下自主增殖，但仅在贴壁细胞存在的情况下。在悬浮培养的低细胞密度和克隆形成试验中，重组粒细胞巨噬细胞集落刺激因子（GM-CSF）和重组白细胞介素-1（IL-1）分别刺激原始细胞生长。抗GM-CSF可抑制对rIL-1的反应（小于90%），提示对IL-1的增殖反应由GM-CSF介导。这一观点得到了实验支持，这些实验表明在IL-1存在下制备的原始细胞条件培养基含有GM-CSF活性，可刺激正常粒细胞-巨噬细胞前体（CFU-GM）和同源GM-CSF反应性AML原始细胞的生长。由于在无外源性IL-1的情况下制备的BCCM中未检测到IL-1但检测到GM-CSF活性，且抗IL-1中和抗体抑制悬浮培养中原始细胞的自主生长，我们得出结论，白血病细胞内源性分泌IL-1刺激自分泌GM-CSF分泌，诱导原始细胞群体的自主生长。
