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Bidirectional effects of transforming growth factor beta (TGF-beta) on
colony-stimulating factor-induced human myelopoiesis in vitro: differential
effects of distinct TGF-beta isoforms
SE Jacobsen, JR Keller, FW Ruscetti, P Kondaiah, AB Roberts and LA Falk
Laboratory of Molecular Immunoregulation, PRI/DynCorp, Frederick, MD.
Transforming growth factor-beta (TGF-beta) has potent antiproliferative
effects on human hematopoietic progenitor cells. We report here that
TGF-beta 1 and -beta 2 also exert bimodal dose-dependent stimulation of
granulocyte-macrophage colony-stimulating factor (CSF) and granulocyte-
CSF-induced day 7 granulocyte-macrophage colony-forming units. This
increase in colony formation was restricted to low doses (0.01 to 1.0
ng/mL) of TGF-beta 1 and was due to increased granulopoiesis, showing that
TGF-beta can affect the differentiation as well as the proliferation of
hematopoietic progenitors. Furthermore, TGF-beta 3 was found to be a more
potent inhibitor of hematopoietic progenitor cells than TGF-beta 1 and
-beta 2. In contrast to the bidirectional proliferative effects of TGF-beta
1 and -beta 2, the effects of TGF- beta 3 on human hematopoiesis were only
inhibitory, showing for the first time that TGF-beta isoforms differ not
only in potencies but also with regard to the nature of the response they
elicit.
Volume 78,
Issue 9,
pp. 2239-2247,
11/01/1991
Copyright © 1991 by The American Society of Hematology
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