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Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on
colony formation by human marrow hematopoietic progenitor cells
HE Broxmeyer, S Cooper, L Lu, G Hangoc, D Anderson, D Cosman, SD Lyman and DE Williams
Department of Medicine (Hematology/Oncology), Indiana University School of
Medicine, Indianapolis 46202-5121.
Purified natural (n) and recombinant (r) murine (mu) mast cell growth
factor (MGF, a c-kit ligand) were evaluated alone and in combination with r
human (hu) erythropoietin (Epo), rhu granulocyte-macrophage
colony-stimulating factor (rhuGM-CSF), rhuG-CSF, and/or rhuM-CSF for
effects in vitro on colony formation by multipotential (colony-forming
unit-granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM]), erythroid
(burst-forming unit erythroid [BFU-E]) and granulocyte- macrophage (CFU-GM)
progenitor cells from normal human bone marrow. MGF was a potent enhancing
cytokine for Epo-dependent CFU-GEMM and BFU-E colony formation, stimulating
more colonies and of a larger size than either rhu interleukin-3 (rhuIL-3)
or rhuGM-CSF. MGF, especially at lower concentrations, also acted with
rhuIL-3 or rhuGM-CSF to enhance Epo-dependent CFU-GEMM and BFU-E colony
formation. MGF had little stimulating activity for CFU-GM colonies by
itself, but in combination with suboptimal to optimal amounts of rhuGM-CSF
enhanced the numbers and the size of CFU-GM colonies in an additive to
greater than additive manner. While we did not detect an effect of MGF on
CFU-G colony numbers stimulated by maximal concentrations of rhuG-CSF, MGF
did enhance the size of CFU-G-derived colonies. MGF did not enhance the
activity of rhuM-CSF. In a comparative assay, maximal concentrations of rmu
and rhuMGF were equally effective in the enhancement of human bone marrow
colony formation, but rhuMGF, in contrast to rmuMGF, did not at the
concentrations tested enhance colony formation by mouse bone marrow cells.
MGF effects on BFU-E, CFU-GM, and CFU-GEMM may be direct acting ones as
MGF-enhanced colony formation by these cells in highly enriched progenitor
cell populations of CD34 HLA-DR+ and CD34 HLA-DR+CD33- sorted cells in
which greater than or equal to 1 of 2 cells was a BFU-E plus CFU-GM plus
CFU-GEMM. MGF appears to be an early acting cytokine that preferentially
stimulates the growth of immature hematopoietic progenitor cells.
Volume 77,
Issue 10,
pp. 2142-2149,
05/15/1991
Copyright © 1991 by The American Society of Hematology
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