DYNAMICS OF THE NUMBER OF M2 MACROPHAGES IN LIVER REGENERATION IN RATS

A.V. Elchaninov (1, 2), T.Kh. Fatkhudinov (1, 2), N.Yu. Usman (1), 2, A.V. Makarov (1, 2),
I.V. Arutyunyan (1, 2), E.Yu. Kananykhina (1, 2), G.B. Bolshakova (2), D.V. Goldstein (3), G.T. Sukhikh (1)
1-V.I. Kulakov Research Center for Obstetrics, Gynecology and Perinatology, Akademika Oparina str, 4, Moscow, 117997, Russian Federation;
2-Scientific Research Institute of Human Morphology, Tsuryupy str., 3, Moscow, 117418, Russian Federation;
3-Research Centre of Medical Genetics, Moskvorechye str., 1, Moscow, 115478, Russian Federation

Introduction. Macrophages are referred to the one of the major cell types that organize the liver regeneration. Macrophages are a heterogeneous cell population. The study of regulatory mechanisms of liver regeneration after subtotal liver resection in rats, considered as a model of the small-for-size syndrome after liver resection presenting in oncology and transplantology, is of theoretic and applied interest. Aim of the research is to study the dynamics of M2 macrophage populations, as well as gene expression il1b, il6, tnfα, associated with M1 macrophages and il-10 gene associated with M2 macrophages during the course of liver regeneration after subtotal resection. Materials and Methods. The model of liver regeneration after subtotal resection in rats was reproduced. Expression of cytokine genes was studied with the use of real-time polymerase chain reaction. Total population of liver macrophages was detected with the use of antibodies to the CD68 marker, M2 macrophages were detected with the use of antibodies to CD206. Results. Subtotal hepatectomy was established to cause a change in state of the total population of liver macrophages in the rats. This is pronounced by the activation of the expression of gene of several cytokines, as well as by the increasing in the total number of macrophages in the liver and the appearance among them subpopulations of cells expressing CD206. Conclusion. In regenerating liver, the source of the delivery of proregenerative macrophages expressing CD206 is monocytes and resident liver macrophages – Kupffer cells. In addition, in regenerating liver the dynamic both of cytokines expression and the number of CD206+ cells indicate to the fact that in lever regeneration polarization of macrophages fails to be observed, probably, due to the early onset of hepatocyte proliferation against background of alterative phase of inflammation.
Keywords: 
liver regeneration; cytokines; macrophages