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Relevance. Currently, the participation of immune system cells in the regulation of reparative processes is attracting more and more attention of researchers. There is an anatomical connection between the liver and spleen by means of portal vein. Thus, cytokines and other biologically active substances can enter the liver from the spleen through the portal vein, as well as cells can migrate to the liver. However, the specific mechanisms of mutual influence of the mentioned organs, including in reparative processes, remain poorly studied. The aim of our work was to study the state of spleen monocyte-macrophage population after liver resection, as well as the proliferative activity of spleen cells during liver regeneration . Materials and Methods . The model of liver regeneration after 70 % resection in mouse was reproduced in this work. The animals were taken out of the experiment after 1, 3 and 7 days. The marker of cell proliferation Ki67 was immunohistochemically detected, the state of spleen monocyte-macrophage population was evaluated by markers CD68, CD115, CD206, F4/80 by methods of immunohistochemistry and flow cytometry. Results and Discussion . The liver regeneration had a pronounced effect on the cytoarchitectonics of the spleen. In 1 day after liver resection in the spleen there was observed a decrease in the share of Ki67+cells, according to the flow cytometry data there was a decrease in the number of CD115+cells, in 3 and 7 days there was a decrease in the number of F4/80+ macrophages. Conclusion . Liver resection causes changes in the state of cell populations of the spleen as well. First of all, to the decrease in the activity of proliferative processes in it, as well as to the changes in the state of the monocyte-macrophage system. A decrease in the content of CD115+ and F4/80+ cells in the spleen was found, which indirectly indicates the migration of monocytes/macrophages after liver resection, which can also influence the course of reparative processes in the liver.

Relevance . Macrophages are the leading regulatory cell-lineage taking part in reparative processes in mammals, and the liver is no exception. The ratio of monocyte migration, proliferation and death of macrophages during liver regeneration requires further studies. The aim was to quantify the intensity of monocyte migration, cell proliferation and apoptosis of resident liver macrophages after its 70 % resection in a mouse model. Materials and Methods. We performed 70 % liver resection in sexually mature male BalbC mice. Cells of liver monocyte-macrophage system were obtained by magnetic sorting by marker F4/80. The immunophenotype of the isolated cells was further studied by cytofluorimetry, the level of proliferation and cell death, the content of cyclins and P53 was determined by western blot. Results and Discussion . It was found that after partial hepatectomy there is a marked migration of monocytes/macrophages positive for Ly6C and CD11b markers to the liver, the migration process starts already in the first day after the operation. On the same terms there is a rise in proliferative activity of macrophages, established by Ki67 marker, the peak of proliferation - 3 days after partial hepatectomy. A significant increase in the number of dying macrophages was found early after liver resection. Conclusion . The obtained data indicate that liver regeneration in mammals on the model in mice is accompanied by proliferation migration and cell death of macrophages. Taking into account the immunophenotype of macrophages, we can conclude that Ly6C+ blood monocytes migrate to the liver, and resident macrophages participate in proliferation. The obtained data confirm the universality of the course of reparative processes in mammals.

Abstract Background In many clinical cases of extensive liver resection (e.g. due to malignancy), the residual portion is too small to maintain the body homeostasis. The resulting acute liver failure is associated with the compensatory growth inhibition, which is a typical manifestation of the ‘small for size’ liver syndrome. The study investigates possible causes of the delayed onset of hepatocyte proliferation after subtotal hepatectomy (80% liver resection) in rats. Results The data indicate that the growth inhibition correlates with delayed upregulation of the Tnf gene expression and low content of the corresponding Tnfα protein within the residual hepatic tissue. Considering the involvement of Tnf/Tnfα, the observed growth inhibition may be related to particular properties of liver macrophages – the resident Kupffer cells with CD68+CX1CR3−CD11b− phenotype. Conclusions The delayed onset of hepatocyte proliferation correlates with low levels of Tnfα in the residual hepatic tissue. The observed growth inhibition possibly reflects specific composition of macrophage population of the liver. It is entirely composed of embryonically-derived Kupffer cells, which express the ‘proregeneratory’ M2 macrophage-specific marker CD206 in the course of regeneration.

Liver diseases are one of the main causes of mortality. In this regard, the development of new ways of reparative processes stimulation is relevant. Macrophages play a leading role in the regulation of liver homeostasis in physiological conditions and in pathology. In this regard, the development of new liver treatment methods is impossible without taking into account this cell population. Resident macrophages of the liver, Kupffer cells, represent a unique cell population, first of all, due to their development. Most of the liver macrophages belong to the self-sustaining macrophage cell population, whose origin is not bone marrow. In addition, Kupffer cells are involved in such processes as regulation of hepatocyte proliferation and apoptosis, remodeling of the intercellular matrix, lipid metabolism, protective function, etc. Such a broad spectrum of liver macrophage functions indicates their high functional plasticity. The review summarizes recent data on the development, phenotypic and functional plasticity, and participation in the reparative processes of liver macrophages: resident macrophages (Kupffer cells) and bone marrow-derived macrophages.