The flt3 ligand supports proliferation of lymphohematopoietic progenitors and early B-lymphoid progenitors.
We have examined the effects of the murine ligand (FL) for the flt3/flk2 tyrosine kinase receptor on the proliferation of murine lymphohematopoietic progenitors as well as committed myeloid and B-cell progenitors. In the presence of erythropoietin, FL alone supported scant colony formation from enriched marrow cells of normal mice. However, when it was combined with interleukin-3 (IL-3), steel factor (SF), or IL-11, FL significantly enhanced colony formation. When tested on enriched marrow cells from 5-fluorouracil (5-FU)-treated mice, FL neither enhanced IL-3-dependent colony formation nor synergized with SF in support of colony formation. However, FL synergized with IL-6, IL-11, or granulocyte-colony stimulating factor (G-CSF) in support of formation of various types of colonies, including multilineage colonies. Approximately 30% of these colonies yielded pre-B-cell colonies when replated in secondary cultures containing SF and IL-7, indicating that 2-cytokine combinations, including FL and IL-6, IL-11, or G-CSF can support the proliferation of primitive lymphohematopoietic progenitors. FL, by itself and in synergy with IL-7 or SF, supported the proliferation of B-cell progenitors. These results show that FL has a wide range of activities in early hematopoiesis and B lymphopoiesis.
Hirayama
F
F
Department of Medicine, Medical University of South Carolina, Charleston, USA.
Lyman
S D
SD
Clark
S C
SC
Ogawa
M
M
D000818:Animals; D001402:B-Lymphocytes; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007378:Interleukins / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D051941:fms-Like Tyrosine Kinase 3
D016298:Hematopoietic Cell Growth Factors; D007378:Interleukins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; C084881:flt3 ligand protein; C497971:Flt3 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3; D005472:Fluorouracil