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Lactoferrin decreases monocyte-induced fibroblast production of myeloid
colony-stimulating activity by suppressing monocyte release of
interleukin-1
JR Zucali, HE Broxmeyer, D Levy and C Morse
Department of Medicine, University of Florida, Gainesville.
Lactoferrin (Lf) is a negative regulator of myelopoiesis which operates by
suppressing the release from mononuclear phagocytes of GM colony-
stimulating factor (GM-CSF) or monokines which can then induce the release
of GM-CSA from accessory cells. In this study, endotoxin- depleted,
purified iron-saturated human Lf was assessed for its effect on the
production of interleukin-1 by cultured monocytes and their subsequent
effect on colony-stimulating factor release from cultured fibroblasts.
Monocytes were grown with or without Lf and Lf that had previously been
incubated with monoclonal anti-Lf. The monocyte- conditioned medium was
then either assayed for the presence of interleukin-1 (IL-1) with an
enzyme-linked immunosorbent assay or for its ability to stimulate
fibroblasts to release growth factors for CFU- GM, BFU-E, or CFU-Mix
colonies. In the presence of Lf (10(-7) or 10(-8) mol/L), GM
colony-stimulating activity (GM-CSA) was suppressed by 31% to 73%, whereas
stimulating activities for BFU-E and CFU-mix colony formation were
suppressed by 93% to 100%. Antibody to Lf completely abrogated the
suppressive effects observed with Lf, whereas antibody to IL-1 ablated the
induction by monocyte-conditioned medium of CSA release by fibroblasts. Lf
at 10(-7) and 10(-8) mol/L also reduced IL-1 synthesis by cultured
monocytes from 60% to 77%. The inhibitory effects of Lf were only observed
when Lf was added before adherence of the monocytes for culture. If Lf was
added at the time of adherence or after adherence, no suppression was
observed. We conclude that the inhibition of GM-CSA production/release by
Lf is mediated through inhibition of the synthesis/release of IL-1 by
mononuclear phagocytes. This inhibition of IL-1 prevents accessory cells
from producing and/or releasing GM-CSA.
Volume 74,
Issue 5,
pp. 1531-1536,
10/01/1989
Copyright © 1989 by The American Society of Hematology
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