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Identification of a growth factor for primary murine stroma as macrophage
colony-stimulating factor
EI Deryugina, BI Ratnikov, MA Bourdon, GL Gilmore, RK Shadduck and CE Muller- Sieburg
La Jolla Institute for Experimental Medicine (LJIEM), CA 92037, USA.
Knowledge of the stromal microenvironment is crucial for understanding the
hematopoietic system. We took advantage of an assay that permits analysis
of primary stroma-initiating cells (SICs) on the clonal level, and further
characterized SICs and the factors that regulate SICs. Stroma formation in
this assay is dependent on a high-molecular-weight factor secreted by the
stromal cell line AC3.U. Here we show that this factor is identical to
macrophage colony-stimulating factor (M-CSF), and that purified M-CSF is
sufficient for induction of stroma formation. M-CSF, isolated from the line
AC3.U, as well as from L929 cells and COS cells transfected with an
expression vector encoding M- CSF, migrated in two peaks as 160- and 650-kD
species after gel filtration. These molecular-weight species encompassed
all stroma- inducing activity, and both stimulated macrophage colony
formation. Affinity chromatography and blocking studies with antibodies
specific for M-CSF and c-fms confirmed M-CSF as the sole factor in the
supernatant of the stromal cell line AC3.U that promotes stroma formation.
Culture of marrow, for as little as 1 week, depleted M-CSF- dependent SIC
while increasing the incidence of replatable, factor- independent SIC. This
suggests that culture changes the properties of SICs, perhaps by inducing
differentiation into mature stromal cells. Thus, our results show a novel
function of M-CSF as an important modulator of stroma formation.
Volume 86,
Issue 7,
pp. 2568-2578,
10/01/1995
Copyright © 1995 by The American Society of Hematology
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