| Abstract: |
Transforming growth factor-β (TGFβ) regulates cell growth and differentiation in numerous cell systems, including several hematopoietic lineages. We used in vitro cultures of highly enriched hematopoietic progenitor cells stimulated by natural and recombinant growth factors to investigate the biologic effects of TGFβ1 and TGFβ2 on erythroid (CFU-E and burst-forming unit (BFU)-E, granulocyte-macrophage (CFU-GM) and multilineage (i.e., granulocyte, erythroid, macrophage, and megakaryocyte; CFU-GEMM) colony-forming cells. In the absence of exogenous CSF, neither TGFβ1 nor TGFβ2 supported progenitor cell growth. In the presence of recombinant or natural CSF, picomolar concentrations of TGFβ1 inhibited growth of CFU-E, BFU-E and CFU-GEMM and enhanced growth of day 7 CFU-GM. Inhibition of CFU-E and BFU-E by human and porcine TGFβ1 was similar, ranging from 17 to 73% over a concentration range of 0.05 to 1.0 ng/ml, and was largely independent of the type of burst-promoting activity used (rIL-3 vs cell 5637-conditioned medium). Inhibition of CFU-GEMM ranged from 79 to 98% over a concentration range of 0.25 to 1.0 ng/ml. The inhibitory effect of TGFβ1 was progressively lost when its addition was delayed for 40 to 120 h, suggesting a mode of action during early cell divisions. In contrast, growth of CFU-GM stimulated by plateau concentrations of human rG-CSF, rGM-CSF, and rIL-3 was enhanced up to 154 ± 22% by human TGFβ1. Porcine platelet-derived TGFβ2 was essentially without effect on the progenitor populations examined. These results support the hypothesis that TGFβ may play a role in the regulation of hematopoietic progenitor cell proliferation by differentially affecting individual lineages and is apparently capable of doing so in the relative absence of marrow accessory cells. |
