title: 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.
abstract: 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.
authors.affiliation: Laboratory of Molecular Immunoregulation, PRI/DynCorp, Frederick, MD.
authors.forename: S E
authors.initials: SE
authors.lastname: Jacobsen
authors.forename: J R
authors.initials: JR
authors.lastname: Keller
authors.forename: F W
authors.initials: FW
authors.lastname: Ruscetti
authors.forename: P
authors.initials: P
authors.lastname: Kondaiah
authors.forename: A B
authors.initials: AB
authors.lastname: Roberts
authors.forename: L A
authors.initials: LA
authors.lastname: Falk
mesh_terms: D002454:Cell Differentiation; D002455:Cell Division; D003114:Colony-Forming Units Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D007377:Interleukin-3; D016212:Transforming Growth Factor beta; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor