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Inducible production of human macrophage growth factor, CSF-1
P Ralph, MK Warren, MT Lee, J Csejtey, JF Weaver, HE Broxmeyer, DE Williams, ER Stanley and ES Kawasaki
A panel of human cell lines was screened for production of colony-
stimulating factor-1 (CSF-1) using a specific radioreceptor assay and
criterion of macrophage colony growth in mouse bone marrow culture. The
pancreatic carcinoma lines MIA PaCa and PANC were found to secrete high
levels of CSF-1. In a bone marrow proliferation assay, the activities from
these two lines were blocked by a CSF-1 specific neutralizing antiserum,
confirming the predominant content of this macrophage growth factor. MIA
PaCA cells stopped secreting CSF-1 when transferred to various serum-free
media. Serum-free production could be reinitiated by phorbol myristic
acetate (PMA). Purified CSF-1 from serum-free MIA PaCa cells stimulated the
formation of 14-day colonies from total and nonadherent mononuclear human
bone marrow cells. Most of the colonies consisted exclusively of large,
dispersed macrophages that were intensely stained for nonspecific esterase.
Although similar numbers of human 14-day colonies were stimulated by CSF-1
and other CSFs, more CSF- 1 was required for the proliferation of human as
compared with murine bone marrow progenitors. Northern analysis of mRNA
from induced-MIA PaCa cells, using a human CSF-1 oligonucleotide probe,
revealed multiple species of CSF-1 mRNA ranging from 1.5 to 4.5 kilobases
(kb). Uninduced, serum-free cultures showed only the largest mRNA species,
suggesting that serum removal interfered with CSF-1 mRNA processing related
to synthesis and/or secretion of the protein. Regulation of the production
of CSF-1 may be an important physiological process in hematopoiesis and
macrophage functioning.
Volume 68,
Issue 3,
pp. 633-639,
09/01/1986
Copyright © 1986 by The American Society of Hematology
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