Lactoferrin decreases monocyte-induced fibroblast production of myeloid colony-stimulating activity by suppressing monocyte release of interleukin-1

J. R. Zucali, Hal Broxmeyer, D. Levy, C. Morse

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1531-1536
Number of pages6
JournalBlood
Volume74
Issue number5
StatePublished - 1989
Externally publishedYes

Fingerprint

Lactoferrin
Fibroblasts
Interleukin-1
Monocytes
Colony-Stimulating Factors
Erythroid Precursor Cells
Accessories
Phagocytes
Conditioned Culture Medium
Myelopoiesis
Monokines
Immunosorbents
Granulocyte-Macrophage Progenitor Cells
Antibodies
Endotoxins
Assays
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Lactoferrin decreases monocyte-induced fibroblast production of myeloid colony-stimulating activity by suppressing monocyte release of interleukin-1. / Zucali, J. R.; Broxmeyer, Hal; Levy, D.; Morse, C.

In: Blood, Vol. 74, No. 5, 1989, p. 1531-1536.

Research output: Contribution to journalArticle

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abstract = "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.",
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