IN VITRO REPROGRAMMING OF NITRIC OXIDE-SYNTHETIC MECHANISMS FOR M1 AND M2 PHENOTYPES OF MURINE PERITONEAL MACROPHAGES: DEPENDENCE ON DIFFERENT SERUM CONCENTRATIONS

Abstract. Macrophages are among key players of inflammatory events, acquiring either pro-inflammatory M1, or anti-inflammatory M2 phenotype, dependent on their microenvironment. Some endogenous macrophagereprogramming factors (MRFs), e.g., TGF-β (an M2-inducing agent), are found in blood serum. This work confirms a hypothesis on in vitro M1-to-M2 phenotype reprogramming of cultured macrophages, by means of decrease or increase in serum concentration. Noteworthy, the macrophages from C57BL/6 и BALB/c mice strains did not differ with their reprogramming capacity. In general, our results allow of extending present knowledge about a role of environmental factors in regulation of macrophage activities.

reprogramming, macrophages, phenotype, nitric oxide

1. Стандарты по диагностике и лечению больных хронической обструктивной болезнью легких (ATS/ERS, пересмотр 2004 г.): Пер. с англ. / Под ред. А.Г. Чучалина. – М.: «Атмосфера», 2005. – 96 с.

2. Хаитов Р.М. Иммунология: учеб. – М.: ГЭОТАР-Медиа, 2006.

3. Biswas S.K., Mantovani А. Macrophages plasticity and interaction with lymphocyte subsets: cancer as a paradigm // Nature Immunology. – 2010. –Vol. 11 – P. 889-896.

4. Mills C.D., Kincaid К., Alt J.M., Heilman M.J., Hill A.M. M-1/M-2 Macrophages and the Th1/Th2 Paradigm // The Journal of Immunology. – 2000. –Vol. 164. – P. 6166-6173.

5. Fritz J., Murphy B.S., Sundareshan V., Cory T.J., Hayes D.I., Anstead M.I., and Feola D.J. M1 and M2 Macrophage activation. Azithromycin alters macrophage phenotype // Journal of Antimicrobial Chemotherapy. – 2008. –Vol. 61 (3). – P. 554-560.

6. Hong W.K., Bast R.S., Hait W., Kufe D.W., Holland J.F., Pollock R.E., Weichselbaum R.R. Holland-Frei Cancer medicine, eighth edition. – PMPH-USA, Ltd., 2010. – P. 271.

7. Janeway C.A., Travers P., Walport M., Shlomchik M. Immunobiology. The immune system in health and disease. – Garland Science Publishing, 2005.

8. Lolmede K., Campana L., Vezzoli M., Bosurgi L., Tonlorenzi R., Clementi E., Bianchi M.E., Cossu G., Manfredi A.A., Brunelli S, Rovere-Querini P. Inflammatory and alternatively activated human macrophages attract vessel-associated stem-cells, relying on separate HMGB1- and MMP9-dependent pathways // Journal of Leukocyte Biology. – 2009. – Vol. 85 (5). – P. 779-787.

9. Mantovani A.. Macrophage diversity and polarization.: in vivo veritas // Blood. – 2006. – Vol. 108(2). – P. 408-409

10. Mantovani A., Sica A., Locatti A. New vistas on macrophage differentiation and activation // European Journal of Immunology. – 2006. – Vol. 37 (1). –P. 14-16.

11. Mantovani A., Sica A., Sozzani S., Allavena P., Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization // Trends Immunol. – 2004. –Vol. 25. – P. 677-686.

12. Martinez F.O., Gordon S., Locati A., Mantovani A. Transcriptional Profiling of the Human Monocyteo-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression // J. Immunol. – 2006. – Vol. 177. – P. 7303-7311.

13. Pons A.R., Noguera A., Blanquer D., Sauleda J., Pons J., Aqusti A.G. Phenotypic characterization of alveolar macrophages and peripheral blood monocytes in COPD // Eur Resp J. – 2005. – Vol. 25 (4). – P. 647-52.

14. Redente E.F., Dwyer-Nield L.D., Barrett B.S., Riches D.W.H., Malkinson A.M. Lung tumor growth is stimulated in IFNγ -/- mice and inhibited in IL-4-Rα -/- mice // Anticancer Research. – 2009. –Vol. 29 (12). – P. 5095-5101.

15. Sieling P.A., Abrams J.S., Yamamura M., Salgame P., Bloom B.R., Rea T.H., and Modlin R.L. Immunosuppressive roles for IL-10 and IL-4 in human infection. In vitro modulation of T cell responses in leprosy // J. Immunol. – 1993. – Vol. 150 (12). – P. 5501-5510.

16. Smith F.S., Titheradge M.A.. Nitric oxide protocols // Methods in molecular biology. – 1998. – Vol. 100. – P. 171-180.

17. Woodruff P.G., Modrek B., Choy D.F., Jia G., Abbas A.R., Ellwanger A., Koth L.L., Arron J.R., Fahy J.V. T-helper type 2-driven inflammation defines major subphenotypes of asthma // Am. J. Respir. Crit. Care Med. – 2009. – Vol. 180 (5). – P. 388-395.

18. Zissel G., Prasse A., Muller-Quernheim J. Sarcoidosis-immunopathogenetic concepts // J. Semin Respir Crit Care Med. – 2007. – Vol. 28 (1). – P. 3-14.