Studies on the efficacy of mast cell growth factor (c-kit ligand) in vitro as well as in vivo.
We tested the ability of recombinant human (rhu) mast cell growth factor (MGF), also known as c-kit ligand, to stimulate the colony formation of human bone marrow cells in semisolid medium alone and in combination with rhu erythropoietin (EPO), rhu Interleukin 3 (IL-3), rhu granulocyte colony stimulating factor (G-CSF) and rhu granulocyte-macrophage colony stimulating factor (GM-CSF). The addition of MGF to cultures containing EPO or EPO + IL-3, GM-CSF and G-CSF, resp., resulted in macroscopic erythroid burst-forming units (BFU-E). Multipotential (colony-forming unit granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM]) progenitors were stimulated by MGF in the presence of EPO. Colony-forming unit granulocyte-macrophage (CFU-GM) were activated by MGF only in combination with GM-CSF. The combination of MGF with EPO was used for synergism studies in healthy cynomolgus monkeys. In the chosen concentration MGF alone had no effect on white blood cell (WBC) counts and on platelets, but a slight effect on reticulocytes. EPO by itself increased reticulocyte counts with no effects on WBC or platelets. The combination of both factors resulted in a significant increase of reticulocytes. No other effects were seen. These studies demonstrate the potent synergistic interaction of MGF and other hematopoietic growth factors.
Hintz-Obertreis
P
P
Research Laboratories of Behringwerke AG, Marburg, Germany.
Weinmann
E
E
Seiler
F R
FR
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004347:Drug Interactions; D004921:Erythropoietin / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007958:Leukocyte Count / Q000187:drug effects; D008252:Macaca fascicularis; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012156:Reticulocytes / Q000166:cytology / Q000187:drug effects; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor