Transforming growth factor beta 1 selectively regulates early murine hematopoietic progenitors and inhibits the growth of IL-3-dependent myeloid leukemia cell lines

Transforming growth factor beta 1 (TGF-beta 1) has been shown to be associated with active centers of hematopoiesis and lymphopoiesis in the developing fetus. Therefore, the effects of TGF-beta 1 on mouse hematopoiesis were studied. TGF-beta 1 is a potent inhibitor of IL-3-induced bone marrow prolif...

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Bibliographic Details
Published in:The Journal of experimental medicine 1988-08, Vol.168 (2), p.737-750
Main Authors: Keller, J R, Mantel, C, Sing, G K, Ellingsworth, L R, Ruscetti, S K, Ruscetti, F W
Format: Article
Language:English
Subjects:
Animals
Bone Marrow Cells
Cell Division - drug effects
Cell Line
Cells, Cultured
Colony-Stimulating Factors - pharmacology
Growth Substances - pharmacology
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - drug effects
Interleukin-3 - pharmacology
Leukemia, Myeloid
Mice
Mice, Inbred BALB C
Peptides - pharmacology
Transforming Growth Factors
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Summary:Transforming growth factor beta 1 (TGF-beta 1) has been shown to be associated with active centers of hematopoiesis and lymphopoiesis in the developing fetus. Therefore, the effects of TGF-beta 1 on mouse hematopoiesis were studied. TGF-beta 1 is a potent inhibitor of IL-3-induced bone marrow proliferation, but it does not inhibit the proliferation induced by granulocyte/macrophage, colony-stimulating factor (CSF), granulocyte CSF, and erythropoietin (Epo). TGF-beta 1 also inhibits IL-3-induced multipotential colony formation of bone marrow cells in soft agar, which includes early erythroid differentiation, while Epo-induced terminal differentiation is unaffected. In addition, IL-3-induced granulocyte/macrophage colonies were inhibited; however, small clusters of differentiated myeloid cells were consistently seen in cultures containing IL-3 and TGF-beta 1. Thus, TGF-beta 1 selectively inhibits early hematopoietic progenitor growth and differentiation but not more mature progenitors. TGF-beta 1 is also a potent inhibitor of IL-3-dependent and -independent myelomonocytic leukemic cell growth, while the more mature erythroid and macrophage leukemias are insensitive. Therefore, TGF-beta 1 functions as a selective regulator of differentiating normal hematopoietic cells, and suppresses myeloid leukemic cell growth.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.168.2.737