Abstract

Macrophages (Mph) are highly plastic cells that are able to change their functional activity (polarization) and perform their functions in different physiological and pathological processes (including cancer). Changes in the functional activity of Mph can occur due to the action of a number of external stimuli (cytokines, colony-stimulating factors, products of microbial synthesis, etc.).
 The aim of the research was to study the effect of lectin from B. subtilis IMV B-7724 on the state of macrophage polarization in intact mice of the Balb/c strain.
 The cytotoxic effect of lectin from B. subtilis IMV B-7724 on the peritoneal Mph of intact Balb/c mice was evaluated in vitro; indices, characterizing the functional activity of Mph with M1 and M2 phenotypes and the levels of STAT-1 and STAT-6 mRNA expression, were determined.
 We have shown that the effect of bacterial lectin on peritoneal Mph is concentration-dependent: ≥0.1 mg/ml is cytotoxic while 0.02 and 0.05 mg/ml is stimulating. At low concentrations of lectin there is observed a significant increase in the ratio of NO production to the arginase activity of Mph (NO/Arg), which is characteristic of Mph with the M1 phenotype. Changes in the expression of STAT transcription factors under the influence of the lectin were similar to the changes, found under the combined action of LPS and IFN-γ on Mph. The detected changes in the functional activity of peritoneal Mph of intact mice under the influence of low concentrations of the lectin may be due to the changes in the expression of transcription factors of the JAK-STAT signaling pathway. Understanding the mechanisms of action of lectin from B. subtilis IMV B-7724 on Mph will open new perspectives for their modulation/polarization

Highlights

  • The development of new methods of therapy, aimed at improving the effectiveness of treatment of cancer patients, is the subject of many modern studies [1]

  • It is a known fact that tumors are able to remodel the microenvironment and facilitate the switching M1 macrophages to the tumor-associated state

  • The aim of the study was to investigate the effects of lectin from B. subtilis IMV B-7724 on the state of polarization of Mph of intact Balb/c mice

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Summary

Introduction

The development of new methods of therapy, aimed at improving the effectiveness of treatment of cancer patients, is the subject of many modern studies [1]. The aim of immunotherapy is to restore and maintain the proper activity of the main effectors of antitumor immunity, the formation of a full-fledged immune response to tumor antigens. It is known, that antitumor immune responses play a significant role in preventing the recurrence and metastasis of the primary tumor. In the study of the effectiveness of biotherapy Mph are thought to be the most promising effectors of natural immunity due to their ability to rapidly change the functional state depending on the stimuli they receive from the local microenvironment. The study of M1↔M2 switching mechanisms and the search for possible ways to regulate the polarization process is one of the important ways for immunotherapy optimization [4, 5]

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