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Cofactors are essential for stem cell factor-dependent growth and
maturation of mast cell progenitors: comparative effects of interleukin- 3
(IL-3), IL-4, IL-10, and fibroblasts
D Rennick, B Hunte, G Holland and L Thompson-Snipes
Department of Immunology, DNAX Research Institute of Molecular and Cellular
Biology, Palo Alto, CA.
Stem cell factor (SCF) possesses many mast cell-stimulating activities,
including the ability to support the growth of mucosal-like mast cells
(MMCs) and connective tissue mast cells (CTMCs). However, this study shows
that, in the absence of accessory cells, SCF does not stimulate the clonal
growth of primitive mast cell progenitors. Nevertheless, SCF exhibited
potent growth-promoting effects when combined with the cytokines
interleukin-3 (IL-3), interleukin-4 (IL-4), and interleukin- 10 (IL-10).
Our comparative studies have shown that optimal mast cell colony formation
occurs when both IL-4 and IL-10 are combined with SCF. However, in the
presence of SCF, these two cofactors appear to mediate different effects.
IL-4 was more efficient than IL-10 in costimulating the initiation of
SCF-dependent colony formation by mast cell progenitors and in sustaining
the proliferation of newly generated progeny. On the other hand, IL-4 was
less efficient than IL-10 in supporting mast cell differentiation, as
evidenced by morphology, cell enlargement, and granule production. Although
the actions of IL-4 and IL-10 were not equivalent, additional experiments
indicated that their ability to serve as early- and late-acting factors,
respectively, were complimentary. We have also found that the mast cells
generated in colonies stimulated by IL-4, IL-10, and SCF produced high
levels of histamine (6-8 pg per cell). None of the mast cells generated in
our cultures synthesized heparin. A phenotypic change from safranin-
negative to safranin-positive cells associated with heparin-producing CTMCs
was accomplished after coculture of the mast cells with fibroblast cell
lines derived from normal mice or from SI/SId mice plus soluble factors.
Collectively, our observations demonstrate that SCF acts as a competence
factor for mast cell progenitor growth. In addition, the ability of SCF to
support certain stages of mast cell differentiation is profoundly
influenced by interactions with specific cofactors.
Volume 85,
Issue 1,
pp. 57-65,
01/01/1995
Copyright © 1995 by The American Society of Hematology
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