Le Bousse-Kerdilès M C, Souyri M, Smadja-Joffe F, Praloran V, Jasmin C, Ziltener H J
Unité d'Oncogènése Appliquée, INSERM U268, Hôpital Paul Brousse, Villejuif, France.
Blood. 1992 Jun 15;79(12):3179-87.
The murine myeloproliferative syndrome induced by the myeloproliferative sarcoma virus (MPSV) has numerous similarities to human primary myelofibrosis. We have shown that medium conditioned by spleen cells of MPSV-infected mice has the capacity to support the growth of primitive blast cell colonies. The detection of this activity associated with MPSV infection stimulated us to characterize the hematopoietins responsible for this activity. Northern blot analysis showed a large increase, or induction, of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage-CSF (CSF-1), and granulocyte-CSF (G-CSF) transcripts in the hematopoietic organs of MPSV-infected mice; however, no IL-3 transcript could be detected in either MPSV-infected or normal mice. Significant levels of IL-1 alpha, IL-6, G-CSF, and CSF-1 bioactivities were found in the serum of MPSV-infected mice, but not in controls. Additionally, analysis of medium conditioned by spleen cells of MPSV-infected mice showed the presence of tumor necrosis factor alpha bioactivity. The increased production of cytokines that are able to stimulate pluripotent hematopoietic stem cells corroborates the hypothesis of a possible involvement of hematopoietic growth factors in the development of some myeloproliferative disorders.
由骨髓增殖性肉瘤病毒(MPSV)诱发的小鼠骨髓增殖综合征与人类原发性骨髓纤维化有许多相似之处。我们已经表明,受MPSV感染小鼠的脾细胞所产生的条件培养基有能力支持原始胚细胞集落的生长。与MPSV感染相关的这种活性的检测促使我们对负责这种活性的造血生长因子进行特性分析。Northern印迹分析显示,在MPSV感染小鼠的造血器官中,白细胞介素-6(IL-6)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、巨噬细胞集落刺激因子(CSF-1)和粒细胞集落刺激因子(G-CSF)的转录物大幅增加或诱导表达;然而,在MPSV感染的小鼠或正常小鼠中均未检测到IL-3转录物。在MPSV感染小鼠的血清中发现了显著水平的IL-1α、IL-6、G-CSF和CSF-1生物活性,但在对照组中未发现。此外,对MPSV感染小鼠的脾细胞所产生的条件培养基的分析显示存在肿瘤坏死因子α生物活性。能够刺激多能造血干细胞的细胞因子产量增加,证实了造血生长因子可能参与某些骨髓增殖性疾病发生发展的假说。