Preview

Medical Immunology (Russia)

Advanced search

DIRECT EFFECTS OF GM-CSF ON THE FUNCTIONS OF HUMAN MONOCYTES/MACROPHAGES

https://doi.org/10.15789/1563-0625-2019-3-419-426

Abstract

We investigated direct effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the surface properties and cytokine-producing activity of human monocytes/macrophages (Mc/Mphs). The CD14+ cells were isolated from peripheral blood of healthy donors by positive magnetic separation. The isolated Mc/Mphs were cultured with lipopolysaccharide (LPS, 1 μg/ml) or without LPS for 24 hours. Membrane expression of CD14, CD16, CD119, CD124, and CD197 molecules was assessed by flow cytometry. The contents of tumor necrosis factor-α (TNFα), interleukin-1β (IL-1β), IL-6 and IL-10 in culture supernatants were determined by the enzyme immunoassay technique. It was found that GM-CSF at a concentration range of 0.01-10 ng/ml did significantly reduce the number of cells expressing CD197 (CC receptor of chemokine 7), without significantly affecting the percentage of CD14+ (coreceptor of LPS), CD16+ (low-affinity Fc receptor), CD119+ (IFNγ receptor) and CD124+ (IL-4 receptor) cells. At the same time, GM-CSF reduced the contents of CD197+ macrophages, as well as CD14+, CD16+, and CD119+ cells among the activated cell population, without significantly altering the number of CD124+ cells. It was also shown that GM-CSF (10 ng/ml), was able to enhance production of TNFα and IL-6, but not IL-1β and IL-10 by activated Mc/Mphs. The results obtained indicate the ability of GM-CSF to exert both anti-inflammatory and pro-inflammatory effects upon macrophage cell populations. In general, such effects could contribute to the development of adaptive immunogenesis in peripheral tissues.

About the Authors

N. D. Gazatova
I. Kant Baltic Federal University
Russian Federation

Research Associate, Center of Medical Biotechnologies

Kaliningrad



M. E. Meniailo
I. Kant Baltic Federal University
Russian Federation

Junior Research Associate, Center of Medical Biotechnologies

Kaliningrad



V. V. Malashchenko
I. Kant Baltic Federal University
Russian Federation

Junior Research Associate, Center of Medical Biotechnologies

Kaliningrad



A. G. Goncharov
I. Kant Baltic Federal University
Russian Federation

PhD (Medicine), Director, Institute of Live Systems

Kaliningrad



O. B. Melashchenko
I. Kant Baltic Federal University
Russian Federation

Research Associate, Center of Medical Biotechnologies

Kaliningrad



E. M. Morozova
I. Kant Baltic Federal University
Russian Federation

Junior Research Associate, Center of Medical Biotechnologies

Kaliningrad



V. I. Seledtsov
I. Kant Baltic Federal University
Russian Federation

PhD, MD (Medicine), Professor, Chief Research Associate, Center of Medical Biotechnologies

236001, Kaliningrad, Gaidar str., 6-406

Phone: 7 (915) 263-60-27



References

1. Kudryavtsev I.V. Memory T cells: major populations and stages of differentiation. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2014, Vol. 8 (17), no. 4, pp. 947-964. (In Russ.)

2. Becher B., Tugues S., Greter M. GM-CSF: from growth factor to central mediator of tissue inflammation. Immunity, 2016, Vol. 45, no. 5, pp. 963-973.

3. Broughton S.E., Nero T.L., Dhagat U., Kan W.L., Hercus T.R., Tvorogov D., Lopez A.F., Parker M.W. The βc receptor family – Structural insights and their functional implications. Cytokine, 2015, Vol. 74, no. 2, pp. 247-258.

4. Codarri L., Gyulveszi G., Tosevski V., Hesske L., Fontana A., Magnenat L., Suter T., Becher B. ROR gamma t drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat. Immunol., 2011, Vol. 12, no. 6 , pp. 560-567.

5. Croxford A.L., Spath S., Becher B. GM-CSF in neuroinflammation: licensing myeloid cells for tissue damage. Trends Immunol., 2015, Vol. 36, no. 10, pp. 651-662.

6. Darrieutort-Laffite C., Boutet M.A., Chatelais M., Brion R., Blanchard F., Heymann D., le Goff B. IL-1β and TNFα promote monocyte viability through the induction of GM-CSF expression by rheumatoid arthritis synovial fibroblasts. Mediators Inflamm., 2014, 241840. doi: 10.1155/2014/241840.

7. El-Behi M., Ciric B., Dai H., Yan Y., Cullimore M., Safavi F., Zhang G.X., Dittel B.N., Rostami A. The encephalitogenicity of T(H) 17 cells is dependent on IL-l- and IL-23-induced production of the cytokine GM-CSF. Nat. Immunol., 2011, Vol. 12, no. 6, pp. 568-575.

8. Eshleman E.M., Delgado C., Kearney S.J., Friedman R.S., Lenz L.L. Down regulation of macrophage IFNGR1 exacerbates systemic L. monocytogenes infection. PLoS Pathog., 2017, Vol. 13, e1006388. doi: 10.1371/journal.ppat.1006388.

9. Geginat J., Sallusto F., Lanzavecchia A. Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4 + T cells. J. Exp. Med., 2001, Vol. 194, no. 12, pp. 1711-1720.

10. Greter M., Helft J., Chow A., Hashimoto D., Mortha A., Agudo-Cantero J., Boqunovic M., Gautier E.L., Miller J., Leboeuf M., Lu G., Aloman C., Brown B.D., Pollard J.W., Xiong H., Randolph G.J., Chipuk J.E., Frenette P.S., Merad M. GM-CSF controls nonlymphoid tissue dendritic cell homeostasis but is dispensable for the differentiation of inflammatory dendritic cells. Immunity, 2012, Vol. 36, no. 6, pp. 1031-1046.

11. Halstead, E. S., Umstead, T. M., Davies, M. L., Kawasawa, Y. I., Silveyra, P., Howyrlak, J., Yang L., Guo W., Hu S., Hewage E.K., Chroneos Z.C. GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization. Resp. Res., 2018, Vol. 19, no. 1, p. 3.

12. Hamilton T.A., Zhao C., Pavicic Jr P. G., Datta S. (2014). Myeloid colony-stimulating factors as regulators of macrophage polarization. Front. Immunol., Vol. 5, p. 554.

13. Hercus T.R., Dhagat U., Kan W.L., Broughton S.E., Nero T.L., Perugini M., Sandow J.J., d’Andrea R.J., Ekert P.G., Hughes T., Parker M.W., Lopez A.F. Signalling by the βc family of cytokines. Cytokine Growth Factor Rev., 2013, Vol. 24, no. 3, pp. 189-201.

14. Hercus T.R., Thomas D., Guthridge M.A., Ekert P.G., King-Scott J., Parker M.W., Lopez A.F. The granulocytemacrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood, 2009, Vol. 114, no. 7, pp. 1289-1298.

15. Hurdayal R., Brombacher F. Interleukin-4 receptor alpha: from innate to adaptive immunity in murine models of Cutaneous Leishmaniasis. Front. Immunol., 2017, Vol. 8, 1354. doi: 10.3389/fimmu.2017.01354.

16. Lau M.Y., Dharmage S.C., Burgess J.A., Win A.K., Lowe A.J., Lodge C., Perret G., Hui J., Thomas P.S., Morrison S., Giles G.G., Hopper J., Abramson M.J., Walters E.H., Matheson M.C. The interaction between farming/ rural environment and TLR2, TLR4, TLR6 and CD14 genetic polymorphisms in relation to early-and late-onset asthma. Sci. Rep., 2017, Vol. 7, 43681. doi: 10.1038/srep43681.

17. Mach N., Gillessen S., Wilson S.B., Sheehan C., Mihm M., Dranoff G. Differences in dendritic cells stimulated in vivoby tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand. Cancer Res., 2000, Vol. 60, no. 12, pp. 3239-3246.

18. Meniailo M.E., Malashchenko V.V., Shmarov V.A., Gazatova N.D., Melashchenko O.B., Goncharov A.G., Seledtsova G.V., Seledtsov V.I. Interleukin-8 favors pro-inflammatory activity of human monocytes/macrophages. Int. Immunopharmacol., 2018, Vol. 56, pp. 217-221.

19. Mukherjee R., Barman P.K., Thatoi P.K., Tripathy R., Das B.K., Ravindran B. Non-classical monocytes display inflammatory features: validation in sepsis and systemic lupus erythematous. Sci. Rep., 2015, Vol. 5, 13886. doi: 10.1038/srep13886.

20. Seledtsov V.I., Seledtsova G.V. A balance between tissue-destructive and tissue-protective immunities: a role of toll-like receptors in regulation of adaptive immunity. Immunobiology, 2012, Vol. 217, no. 4, pp. 430-435.

21. Shapouri-Moghaddam A., Mohammadian S., Vazini H., Taghadosi M., Esmaeili S.A., Mardani F., Seifi B., Mohammadi A., Afshari J.T., Sahebkar, A. Macrophage plasticity, polarization, and function in health and disease. J. Cell. Physiol., 2018, Vol. 233, no. 9, pp. 6425-6440.

22. Shiomi A., Usui T. Pivotal roles of GM-CSF in autoimmunity and inflammation. Mediators Inflamm., 2015, Vol. 2015, 568543. doi:10.1155/2015/568543.

23. Sielska M., Przanowski P., Wylot B., Gabrusiewicz K., Maleszewska M., Kijewska M., Zawadzka M., Kucharska J., Vinnakota K., Kettenmann H., Kotulska K., Grajkowska W., Kaminska B. Distinct roles of CSF family cytokines in macrophage infiltration and activation in glioma progression and injury response. J. Pathol., 2013, Vol. 230, no. 3, pp. 310-321.

24. Son Y., Kim B.Y., Park Y.C., Kim K. Diclofenac Inhibits 27-hydroxycholesterol-induced differentiation of monocytic cells into mature dendritic cells. Immune Netw., 2017, Vol. 17, no. 3, pp. 179-185.

25. van de Laar L., Coffer P.J., Woltman A.M. Regulation of dendritic cell development by GM-CSF: molecular control and implications for immune homeostasis and therapy. Blood, 2012, Vol. 119, no. 15, pp. 3383-3393.

26. Vogel D.Y., Glim J.E., Stavenuiter A.W., Breur M., Heijnen P., Amor S., Dijkstra C.D., Beelen R.H. Human macrophage polarization in vitro:maturation and activation methods compared. Immunobiology, 2014, Vol. 219, no. 9, pp. 695-703.

27. Wicks I.P., Roberts A.W. Targeting GM-CSF in inflammatory diseases. Nat. Rev. Rheumatol., 2016, Vol. 12. no. 1, pp. 37-48.


Review

For citations:


Gazatova N.D., Meniailo M.E., Malashchenko V.V., Goncharov A.G., Melashchenko O.B., Morozova E.M., Seledtsov V.I. DIRECT EFFECTS OF GM-CSF ON THE FUNCTIONS OF HUMAN MONOCYTES/MACROPHAGES. Medical Immunology (Russia). 2019;21(3):419-426. (In Russ.) https://doi.org/10.15789/1563-0625-2019-3-419-426

Views: 1384


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1563-0625 (Print)
ISSN 2313-741X (Online)