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Effect of c-kit ligand on in vitro human megakaryocytopoiesis
RA Briddell, E Bruno, RJ Cooper, JE Brandt and R Hoffman
Department of Medicine, Indiana University School of Medicine,
Indianapolis.
An evaluation of the effects of a recombinant, soluble form of the c- kit
ligand alone and in combination with either granulocyte-macrophage
colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) on the
regulation of human megakaryocytopoiesis was performed using a serum-
depleted clonal assay system and a long-term bone marrow culture system.
The effects of the c-kit ligand on the primitive megakaryocyte (MK)
progenitor cell, the burst-forming unit-megakaryocyte (BFU-MK), and the
more differentiated colony-forming unit-megakaryocyte (CFU-MK) were
determined. The c-kit ligand alone had no megakaryocyte colony- stimulating
activity (MK-CSA) but was capable of augmenting the MK-CSA of both GM-CSF
and IL-3. The range of synergistic interactions of c-kit ligand varied with
the class of MK progenitor cell assayed. In the case of the BFU-MK, the
c-kit ligand synergistically augmented the numbers of colonies formed in
the presence of IL-3, but not GM-CSF, but increased the size of
BFU-MK-derived colonies cloned in the presence of both of these cytokines.
However, at the level of the CFU-MK, c-kit ligand synergized with both
GM-CSF and IL-3 by increasing both colony numbers and size. Although the
c-kit ligand alone exhibited limited potential in sustaining long-term
megakaryocytopoiesis in vitro, it synergistically augmented the ability of
IL-3, but not GM-CSF, to promote long-term megakaryocytopoiesis. These data
indicate that multiple cytokines are necessary to optimally stimulate the
proliferation of both classes of MK progenitor cells and that the c-kit
ligand plays a significant role in this process by amplifying the MK- CSA
of both GM-CSF and IL-3.
Volume 78,
Issue 11,
pp. 2854-2859,
12/01/1991
Copyright © 1991 by The American Society of Hematology
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