RUDN study reveals macrophage dynamics in the regenerating liver after resection

RUDN University discovered the features of liver macrophages activation during its regeneration. In future, it can be used to develop new treatment methods for liver cirrhosis. The results are published in the Biomedicine.

The liver is one of the few mammalian organs capable of regeneration. Macrophages play a key role both in regeneration and in the development of pathological conditions of the liver. In this regard, the mechanisms of activation of liver macrophages continue to be intensively studied. The study used a classical model of mammalian liver regeneration - recovery of liver mass after 70% resection in laboratory mice.

The aim of this research was to study specifically the state of the population of resident liver macrophages, as we previously found that after partial hepatectomy, monocytes/macrophages of bone marrow origin migrate to the remaining liver lobes after resection."

Andrey Elchaninov, MD, PhD, Researcher, Department of Histology, Cytology and Embryology, RUDN University

The work was carried out using the most up-to-date methods: macrophages from the regenerating liver were isolated using the magnetic sorting method, then the expression of marker genes of resident liver macrophages was studied in real time by PCR, and the content of the corresponding proteins was studied by Western blotting, immunocytochemistry, and immunohistochemistry methods.

It was found that the next day after the operation, the number of resident macrophages synthesizing the MARCO protein (Macrophage Receptor with COllagenous structure) almost doubled. The scientists assumed that after liver resection due to the migration of "new" macrophages of bone marrow origin into it, the amount of MARCO protein would decrease. However, this did not happen, which indicates a pronounced induction of MARCO synthesis in liver macrophages after its resection. With the help of the MARCO protein, macrophages bind pathogens and quickly move them inside themselves. At the same time, during liver regeneration, an increase in MARCO synthesis in macrophages is not associated with bacterial infection but reflects the activation of macrophages after liver resection. Given the high level of MARCO synthesis by liver macrophages after its 70% resection, this protein can be used as a target to modify the activity of liver macrophages in its pathological conditions.

"The clinical significance of the obtained data may lie in the fact that resident macrophages of the liver play a key role in the regulation of its homeostasis in normal conditions, during regeneration, and are also closely related to the development of such pathological processes as liver tumors and cirrhosis. Since after liver resection, a pronounced activation of Marco expression occurs, while organotypic regeneration of the parenchyma is observed without excessive deposition of collagen, the stimulation of MARCO synthesis in macrophages can likely be used as a possible target to stimulate the repair of the liver parenchyma and degradation of excessive deposits of the extracellular matrix and collagen in liver cirrhosis», said Andrey Elchaninov, MD, PhD, researcher at the Department of Histology, Cytology and Embryology of RUDN University.