PMID: 9546318Apr 18, 1998Paper

Distinct actions of Flt3 ligand and stem cell factor on myeloid lineage selection and maturation of granulocytes versus macrophages

Experimental Hematology
K DannaeusJ I Jönsson

Abstract

Flt3/Flk2 ligand (FL) and stem cell factor (SCF; c-kit ligand) interact with different but related surface receptor tyrosine kinases expressed on early hematopoietic cells. Both FL and SCF stimulate the proliferation of stem cells and progenitors, but the mechanisms by which these cytokines exert their functions are currently unknown. Here we show that FL and SCF have different effects on myeloid differentiation and lineage selection of early hematopoietic cells using a defined subpopulation of mouse bone marrow (BM) expressing c-Kit but lacking mature lineage markers (c-Kit+Lin-). SCF, together with IL-6, induced the differentiation of a large fraction of these progenitor cells toward mature granulocytes and to a lesser extent toward monocytes. In contrast, FL combined with IL-6 favored differentiation into mature monocytes and macrophages, and very few if any granulocytes could be identified. When FL and SCF were analyzed for their ability to support growth of multilineage erythroid colonies (pre-CFCmulti) and myeloid-committed colony-forming progenitors of granulocytes and monocytes (CFC-G/M), a clear discrepancy was also found. Both FL and SCF had synergistic effects on the proliferation of immature cells with blast-like mo...Continue Reading

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