Pure human hematopoietic progenitors: direct inhibitory effect of transforming growth factors-beta 1 and -beta 2.
TGF-beta 1 and TGF-beta 2 are effective inhibitors of hematopoiesis. We report that colony formation by pure peripheral blood CD34+CD33- BFU-E and CFU-GM (100 cells/dish) is effectively inhibited by both molecules, although TGF-beta 1 is up to 10-fold more potent than TGF-beta 2. Therefore, the effect of these molecules is apparently direct, rather than mediated by accessory cells. The maximal inhibitory activity of TGF-beta is exerted essentially at the early progenitor level, whereas BFU-E/CFU-GM primed for 48 h and IL-3, GM-CSF, and erythropoietin become insensitive to its action. In addition, [3H]TdR suicide experiments indicate that TGF-beta 2 blocks the IL-3-induced progression of early progenitors into the S phase of the cell cycle, whereas IL-6 and bFGF potentiate their entry into the mitotic process. Altogether, these results are compatible with the hypothesis that TGF-beta plays a relevant regulatory role in the homeostasis of early hematopoietic proliferation/differentiation.
Sargiacomo
M
M
Department of Hematology-Oncology, Istituto Superiore di Sanità, Rome, Italy.
Valtieri
M
M
Gabbianelli
M
M
Pelosi
E
E
Testa
U
U
Camagna
A
A
Peschle
C
C
D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007377:Interleukin-3; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor