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Direct stimulation of cells expressing receptors for macrophage colony-
stimulating factor (CSF-1) by a plasma membrane-bound precursor of human
CSF-1
J Stein, GV Borzillo and CW Rettenmier
Department of Hematology/Oncology, St Jude Children's Research Hospital,
Memphis, TN.
Secreted forms of macrophage colony-stimulating factor (M-CSF or CSF-1) are
generated by proteolytic cleavage of membrane-bound glycoprotein
precursors. Alternatively spliced transcripts of the human CSF-1 gene
encode at least two different transmembrane precursors that are
differentially processed in mammalian expression systems. The larger
precursor rapidly undergoes proteolysis to yield the secreted growth factor
and does not give rise to forms of CSF-1 detected on the cell surface. By
contrast, the smaller human CSF-1 precursor is stably expressed on the
plasma membrane where it is inefficiently cleaved to release a soluble
molecule. To determine whether the smaller precursor is biologically active
on the cell surface, mouse NIH-3T3 fibroblasts expressing the different
forms of human CSF-1 were killed by chemical fixation and tested for their
ability to support the proliferation of cells that require this growth
factor. Only fixed cells expressing human CSF-1 precursors on their surface
stimulated the growth in vitro of a murine macrophage cell line or normal
mouse bone marrow-derived mononuclear phagocytes. The ability of these
nonviable fibroblasts to induce the proliferation of CSF-1-dependent cells
was not mediated by release of soluble growth factor, required direct
contact with the target cells, and was blocked by neutralizing antiserum to
CSF-1. These results demonstrate that the cell surface form of the human
CSF-1 precursor is biologically active and indicate that plasma membrane-
bound growth factors can functionally interact with receptor-bearing
targets by direct cell-cell contact.
Volume 76,
Issue 7,
pp. 1308-1314,
10/01/1990
Copyright © 1990 by The American Society of Hematology
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