Summary
The effects of granulocyte colony-stimulation-factor (G-CSF) on stem cell mobilization and its impact on the amplification of myeloid-derived suppressor cells (MDSCs) of donor mice were examined. A mouse model of stem cell mobilization was established by consecutive subcutaneous injection of 100 μg/kg G-CSF for 5 days. The blood from the donor mice was routinely examined during mobilization. Stem cells and MDSCs were analyzed by flow cytometry. The immunosuppressive molecules derived from MDSCs in serum and spleen, including hydrogen dioxide (H2O2) and nitric oxide (NO), and the activity of nitric oxide synthase (NOS) were determined during the mobilization. Apoptosis of T lymphocytes was assessed by using Annexin-V/PI. During stem cell mobilization, the number of lymphocytes and white blood cells in the peripheral blood was increased, and peaked on the 4th day. The number of stem cells in G-CSF-treated mice was significantly greater than that in controls (P<0.01). The expansions of MSDCs were also observed after G-CSF mobilization, with a more notable rate of growth in the peripheral blood than in the spleen. The activity of NOS and the production of NO were increased in the donor mice, and the serum H2O2 levels were approximately 4-fold greater than the controls. Consequently, apoptosis of T lymphocytes was increased and showed a positive correlation with the elevated percentage of MDSCs. It was concluded that G-CSF could provide sufficient peripheral blood stem cells for transplantation. Exogenous administration of G-CSF caused the accumulation of MDSCs in the peripheral blood and the spleen, which could lead to apoptosis of T lymphocytes and may offer a new strategy for the prevention and treatment of graft versus host disease.
Similar content being viewed by others
References
Paczesny S. Discovery and validation of graft-versus-host disease biomarkers. Blood, 2013,121(4):585–594
Gratwohl A, Baldomero H, Horisberger B, et al. Current trends in hematopoietic stem cell transplantation in Europe. Blood, 2002,100(7):2374–2386
Goni O, Alcaide P, Fresno M. Immunosuppression during acute Trypanosoma cruzi infection: involvement of Ly6G (Gr1 (+)) CD11b(+) immature myeloid suppressor cells. Int Immunol, 2002,14(10):1125–1134
Arpinati M, Green CL, Heimfeld S, et al. Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells. Blood, 2000,95(8):2484–2490
Cauley LS, Miller EE, Yen M, et al. Superantigeninduced CD4 T cell tolerance mediated by myeloid cells and IFN-gamma. J Immunol, 2000,165(11):6056–6066
Ezernitchi AV, Vaknin I, Cohen-Daniel L, et al. TCR zeta downregulation under chronic inflammation is mediated by myeloid suppressor cells differentially distributed between various lymphatic organs. J Immunol, 2006,177(7):4763–4772
Wang D, Yu Y, Haarberg K, et al. Dynamic change and impact of myeloid-derived suppressor cells in allogeneic bone marrow transplantation in mice. Biol Blood Marrow Transplant, 2013,19(5):692–702
Highfill SL, Rodriguez PC, Zhou Q, et al. Bone marrow myeloid-derived suppressor cells (MDSC) inhibit graft-versus-host disease (GVHD) via an arginase-1 dependent mechanism that is upregulated by IL-13. Blood, 2010,116(25):5738–5747
Cashen AF, Lazarus HM, Devine SM. Mobilizing stem cells from normal donors: is it possible to improve upon G-CSF? Bone Marrow Transplant, 2007,39(10):577–588
Lemoli RM. New strategies for stem cell mobilization. Mediterr J Hematol Infect Dis, 2012,4(1):e2012066
Rossetti M, Gregori S, Roncarolo MG, et al. Granulocytecolony stimulating factor drives the in vitro differentiation of human dendritic cells that induce anergy in naïve T cells. Eur J Immunol, 2010,40(11):3097–3106
Zeng D, Dejbakhsh-Jones S, Strober S, et al. Granulocyte colony stimulating factor reduces the capacity of blood mononuclear cells to induce graft-versus-host disease: Impact on blood progenitor cell transportation. Blood, 1997,90(1):453–463
Lechner MG, Liebertz DJ, Epstein AL, et al. Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. J Immunol, 2010,185(4):2273–2284
Kusmartsev S, Gabrilovich DI. Role of immature myeloid cells in mechanisms of immune evasion in cancer. Cancer Immunol Immunother, 2008,55(3):237–245
Dugast AS, Haudebourg T, Coulon F, et al. Myeloidderived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion. J Immunol, 2008,180(12):7898–7906
Author information
Authors and Affiliations
Corresponding authors
Additional information
This project was supported by grants from Department of Health of Hubei Province (No. JX5B07) and Department of Health of Wuhan (No. WX09B02).
Rights and permissions
About this article
Cite this article
Zhu, Xj., Hu, J., Sun, L. et al. Amplification of functional myeloid-derived suppressor cells during stem cell mobilization induced by granulocyte colony-stimulation-factor. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 33, 817–821 (2013). https://doi.org/10.1007/s11596-013-1204-x
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-013-1204-x