Monocytes and macrophages show marked phenotypic variation dependent o
n their tissue of origin. Peripheral blood monocytes have been found t
o be sources of a variety of cytokines, but isolated marrow macrophage
s have not been characterized in this regard. Marrow macrophages form
a predominant component of murine adherent Dexter stromal cells and ca
n be isolated by sequential explant culture in colony-stimulating fact
or-1 (CSF-1). We have studied murine (Balb/c) bone marrow macrophage (
BMM) cytokine production in the presence or absence of CSF-1, the lect
in pokeweed mitogen (PWM) or interleukin-3 (IL-3). Biologic activity i
n conditioned media (cm) from control and induced BMM was assessed usi
ng the factor-dependent cell lines 32D, NFS-60, T1165, MC-6 and FDC-P1
. Cell line stimulation and antibody blocking indicated the presence o
f c-kit ligand, interleukin-6 (IL-6) and granulocyte colony-stimulatin
g factor (G-CSF). This stimulatory activity was increased by exposure
to PWM or the combination of CSF-1 and PWM or CSF-1 and IL-3. CSF-1, a
s determined by radioimmunoassay (RIA), was essentially undetectable i
n baseline cm and induction was not seen with PWM or CSF-1. Baseline o
r ''constitutive'' expression of BMM mRNA for CSF-1 and c-kit ligand w
as seen. Uninduced BMM did not express mRNA for G-CSF, granulocyte-mac
rophage CSF (GMCSF), IL-6 or IL-3. CSF-1 induced increased expression
of IL-6 mRNA, PWM induced increased expression of G-CSF and IL-6 mRNA
and the combination of PWM and CSF-1 induced expression of CSF-1, G-CS
F and IL-6 mRNA. Varying levels of CSF-1 had differential effects on c
ytokine production. Increasing levels of CSF-1 increased IL-6 mRNA and
downmodulated CSF-1 mRNA expression. There was a biphasic response of
c-kit ligand mRNA expression to CSF-1 exposure; low levels of CSF-1 (
50 U/mL) induced, while higher levels (2000 U/mL) inhibited, expressio
n.