Human monocytes express functional receptors for granulocyte colony- stimulating factor that mediate suppression of monokines and interferon-γ

Eva Maria Boneberg, Lars Hareng, Florian Gantner, Albrecht Wendel, Thomas Hartung

Research output: Contribution to journalArticlepeer-review

Abstract

In a double-blind, placebo-controlled, randomized study, 10 healthy men received either a single dose of 480 μg granulocyte colony-stimulating factor (G-CSF) or saline. Blood taken from the volunteers was stimulated with 10 μg/mL endotoxin and released cytokines were measured by enzyme-linked immunosorbent assay. Expression of G-CSF receptors on leukocytes was examined by flow cytometry and reverse transcriptase-polymerase chain reaction. Functional activity of these receptors was tested by challenging isolated leukocyte populations to release cytokines with endotoxin in the presence of G-CSF. The G-CSF treatment attenuated the release of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β, and interferon (IFN)-γ, in ex vivo lipopolysaccharide (LPS)-stimulated whole blood. In blood from untreated volunteers the presence of G-CSF in vitro also attenuated the LPS-stimulated release of these cytokines. G-CSF in vitro also attenuated TNF-α release from elutriation-purified monocytes. In the presence of 10 ng/mL recombinant TNF-α, the attenuation of LPS-inducible IFN-γ, release by G-CSF was blunted in whole blood. However, G-CSF had no such effect on IFN-γ release from isolated lymphocytes stimulated with anti- CD3 or a combination of TNF-α and IL-12. G-CSF receptor expression was detected in human neutrophils and monocytes but not in lymphocytes by means of RT-PCR as well as flow cytometry. These results indicate that G-CSF receptors expressed on monocytes are functional in modulating monokine release. We conclude that the attenuation of IFN-γ release from lymphocytes is not a direct effect of G-CSF on these cells but is rather due to the inhibition of monocytic IL-12 and TNF-α release by G-CSF.

Original languageEnglish (US)
Pages (from-to)270-276
Number of pages7
JournalBlood
Volume95
Issue number1
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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