Volume 51, Issue 2 pp. 293-305

Granulocyte–colony-stimulatory factor: a strong inhibitor of natural killer cell function

Laura Schlahsa

Laura Schlahsa

From the Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.

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Yarúa Jaimes

Yarúa Jaimes

From the Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.

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Rainer Blasczyk

Rainer Blasczyk

From the Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.

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Constança Figueiredo

Constança Figueiredo

From the Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.

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First published: 16 August 2010
Citations: 40
Rainer Blasczyk, Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany; e-mail: [email protected].

Abstract

BACKGROUND: The human cytokine granulocyte–colony stimulatory factor (G-CSF) has found widespread application in the medical treatment of neutropenia and to mobilize hematopoietic stem cells used for transplantation. So far, the effect of G-CSF on natural killer (NK) cells has not been fully investigated.

STUDY DESIGN AND METHODS: The effect of G-CSF on the phenotype, cytokine secretion profile, and cytotoxicity of NK cells was assessed. NK cells incubated in vitro in presence of G-CSF for 48 hours as well as NK cells isolated from peripheral blood of G-CSF–mobilized stem cell donors (in vivo) were used.

RESULTS: In vitro, G-CSF caused a strongly altered phenotype in NK cells with 49% down regulation of NKp44 frequency. Furthermore, the expression of the activating receptors NKp46 and NKG2D decreased 40 and 64%, respectively. The expression of KIR2DL1 and KIR2DL2 decreased by 46% each. In cytotoxicity assays, the lytic capacity of G-CSF–exposed NK cells is reduced by up to 68% in vitro and up to 83% in vivo. Accordingly, granzyme B levels of in vivo G-CSF–exposed NK cells were reduced by up to 87% in comparison to nonstimulated NK cells. Cytokine production of in vitro and in vivo incubated NK cells was strongly decreased for interferon-γ, tumor necrosis factor-α, and granulocyte macrophage colony-stimulating factor as well as interleukin (IL)-6 and IL-8. Furthermore, we observed a reduction in proliferation and a positive feedback loop that increased the expression of the G-CSF receptor.

CONCLUSION: G-CSF was demonstrated to be a strong inhibitor of NK cells activity and may prevent their graft-versus-leukemia effect after transplantation.

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