Enhanced hematopoietic growth factor production in an experimental myeloproliferative syndrome.
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.
Le Bousse-Kerdilès
M C
MC
Unité d'Oncogènése Appliquée, INSERM U268, Hôpital Paul Brousse, Villejuif, France.
Souyri
M
M
Smadja-Joffe
F
F
Praloran
V
V
Jasmin
C
C
Ziltener
H J
HJ
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D016298:Hematopoietic Cell Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009196:Myeloproliferative Disorders / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012192:Retroviridae Infections; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016298:Hematopoietic Cell Growth Factors; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor