Basic fibroblast growth factor (B-FGF) induces early- (CFU-s) and late-stage hematopoietic progenitor cell colony formation (CFU-gm, CFU-meg, and BFU-e) by synergizing with GM-CSF, Meg-CSF, and erythropoietin, and is a radioprotective agent in vitro.
Basic fibroblastic growth factor (B-FGF) is a hormone-like protein which belongs to a class of heparin-binding growth factors. B-FGF is synthesized and released to circulate in the blood where it can be recognized by target cells through specific high-affinity plasma membrane receptors. B-FGF is known to be a potent mitogen for a number of specific cell types. We report data which demonstrates B-FGF can influence noncommited and specific lineage-derived hematopoietic progenitors when incubated in vitro. When combined with adherent cell-depleted normal murine marrow cells, B-FGF increased the number of both day 9 and day 12 spleen colony-forming units (CFU-s) from lethally irradiated animals. However, day 12-derived CFU-s were more sensitive to B-FGF, since optimal CFU-s production was observed at 10 ng/ml vs. 100 ng/ml for day 9 CFU-s (p less than 0.05). In adherent cell-depleted murine and human marrow cultures, the addition of B-FGF possessed synergistic activity in combination with the optimal concentration of GM-CSF for CFU-gm at a dose of 10 ng/ml which was inhibited in the presence of protamine sulfate (LD50 dose, 100 mu gm/ml), an inhibitor of B-FGF mitogenic activity, or in the presence of heparin (LD50 dose, 100 U/ml), an effective B-FGF binding agent. B-FGF also expressed synergistic activity in the presence of optimal concentrations of erythropoietin and Meg-CSF for murine and human BFU-e, and murine CFU-meg. No in vitro colony formation was observed when cells were cultured in the presence of B-FGF, but in the absence of the specific hematopoietic growth factor. Finally, B-FGF was also shown to be an effective radioprotective agent in vitro. Murine and human CFU-gm exposed to increasing doses of radiation (0.5 to 5 Gy) combined with GM-CSF and increasing doses of B-FGF (0.1 to 100 ng/ml) produced less radiation-induced toxicity compared to cultures containing GM-CSF alone. This data demonstrates B-FGF influences early- and late-stage hematopoietic progenitors, possesses synergistic activity with hematopoietic growth factors, and is a radioprotective agent in vitro. These results suggest B-FGF must be considered as a member of the family of molecules capable of influencing hematopoiesis in vitro.
Gallicchio
V S
VS
Department of Medicine, Lucille P. Markey Cancer Center, University of Kentucky Medical Center, Lexington 40536-0084.
Hughes
N K
NK
Hulette
B C
BC
DellaPuca
R
R
Noblitt
L
L
D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002588:Cesium Radioisotopes; D004357:Drug Synergism; D004921:Erythropoietin / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D058851:GPI-Linked Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D000090204:Mesothelin; D051379:Mice; D008809:Mice, Inbred C3H; D011479:Protamines / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D013154:Spleen / Q000166:cytology
D002588:Cesium Radioisotopes; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D011479:Protamines; D011506:Proteins; D011837:Radiation-Protective Agents; D016222:Fibroblast Growth Factor 2; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006493:Heparin; D000090204:Mesothelin