Newswise — Researchers at the Research Institute of Molecular and Cellular Medicine of RUDN University have found that with significant damage to the liver, the spleen begins to actively help its neighbor in the abdominal cavity. It shares immune cells and triggers anti-inflammatory processes. The results were published in Frontiers in Cell and Developmental Biology.
Liver recovery largely depends on the immune system. It is known that a key role is played by the spleen, which is directly connected to the liver through the portal vein. However, the exact mechanism of that influence is unknown. Researchers from RUDN University and colleagues from Russian universities studied the changes occurring at the cellular and molecular level in the spleen tissue after liver resection and how this can affect liver recovery.
“The direct anatomical connection between the liver and spleen ensures a coordinated response of these organs to infection, trauma, toxic and other types of damage. The basis of this interaction is not only the general blood circulation between them, but also the common barrier and immune functions. However, despite the direct connection between the liver and spleen, the specific mechanisms of their mutual influence remain poorly understood,” Andrey Elchaninov, Doctor of Medical Sciences, head of the Laboratory of Experimental Morphology, Research Institute of Molecular and Cellular Medicine, RUDN University, said.
The work was performed on laboratory mice. They had 70% of their liver removed, and then the condition of the spleen was examined one day, three days, and a week after that. The authors conducted transcriptomic and immunohistochemical analyses, and the composition of cell populations was also studied using flow cytometry. The methods used make it possible to determine the level of gene expression in the spleen - that is, to understand which processes are activated or slowed down. The second one helps study the markers of cell proliferation and quantity changes of certain spleen cells - lymphocytes, and macrophages.
Loss of 70% of the liver affected the cellular and functional parameters of the spleen. Just one day after surgery, the number of cells positive for the proliferation marker Ki-67 decreased significantly, and the number of CD115+ and Ly6C+ monocytes, as well as the number of macrophages decreased. The expression of the Serpina3n, Stfa2, and Stfa2l1 genes, responsible for serine protease inhibitors synthesis, was also activated. According to modern data, serine protease inhibitors are involved in the regulation of many processes, including the suppression of the inflammatory response.
“A sharp decrease in liver mass significantly affects the spleen. The high level of expression of genes for serine protease inhibitors probably indicates that their synthesis is increased in the spleen, from where they enter the resected liver through the portal circulation, where they take part in inflammation suppressing. A temporary decrease in the number of macrophages and monocytes in the spleen indicates their migration to the liver,” Andrey Elchaninov, Doctor of Medical Sciences, head of the Laboratory of Experimental Morphology, Research Institute of Molecular and Cellular Medicine, RUDN University, said.
RSS