Flt3 ligand can promote survival and macrophage development without proliferation in myeloid progenitor cells

Flt3 ligand elicits a variety of effects on early hemopoietic progenitors b y occupying its cognate receptor, Flt3, a member of the type III tyrosine k inase receptor family, The cytokines macrophage colony-stimulating factor ( RI-CSF) and stem cell factor (SCF) bind to related members of this tyrosine kinase receptors family, c-fms and c-kit, respectively, The relative effec ts of the cytokines M-CSF, SCF, and Flt3L on the proliferation and developm ent of the late myeloid progenitors granulocyte-macrophage colony-forming c ells (GM-CFC) were investigated, Distinct biologic responses were stimulate d by ligand binding to these different tyrosine kinase receptors in enriche d GM-CFC, M-CSF stimulated GM-CFC to proliferate and develop into macrophag es, SCF, on the other hand, stimulated GM-CFC to develop into neutrophils, Flt3 ligand had a relatively small proliferative effect on enriched GM-CFC compared to SCF and M-CSF and had no ability to either stimulate colony for mation or synergize with these two cytokines in promoting DNA synthesis, co lony formation, or expansion in liquid culture. Flt3 ligand, however, was c apable of maintaining the clonogenic potential of GM-CFC and acted as an an ti-apoptotic agent as assessed using the Annexin-V apoptosis assay. GM-CFC cultured in Flt3 ligand eventually formed macrophages and neutrophils in li quid culture. Labeling with the membrane-associated cell tracker dye PKH26 indicated that the majority of the enriched GM-CFC responded to Flt3 ligand by undergoing limited proliferation and macrophage development, whereas ot her cells survived but did not proliferate and differentiate into macrophag es, Thus, Flt3 ligand promoted survival and stimulated development without proliferation in primary-enriched myeloid progenitor cells. (C) 1999 Intern ational Society for Experimental Hematology, Published by Elsevier Science Inc.