Influence of bacterial lectin on key regulatory links of functional activity of macrophages in mice with Ehrlich carcinoma.

Abstract

Recent studies have shown the potential of using different approaches for immunotherapy in cancer treatment. Macrophages (Mph) are one of the promising targets for immunotherapy. To investigate changes in the functional activity of Mph in mice with Ehrlich carcinoma by nitric oxide (NO)/arginase (Arg), IRF4/IRF5and STAT1/STAT6ratios caused by administration of lectin from B. subtilis IMV-7724. From the 2nd day after Ehrlich carcinoma inoculation into female Balb/c mice, lectin from B. subtilis IMV B-7724 (0.02mg/mouse) was administered for 10days. The peritoneal Mph were isolated on days 14, 21, and 28after tumor transplantation and their functional state (NO production, Arg activity and cytotoxic activity) was examined. The levels of mRNA expression of transcription factors STAT-1, STAT-6, IRF5, IRF4were evaluated. In lectin-treated animals with Ehrlich carcinoma, the functional state of Mph (NO/Arg ratio, index of cytotoxic activity) was maintained at the level of intact mice exceeding the values in untreated animals with Ehrlich carcinoma at late terms of tumor growth (21, 28days). Analysis of mRNA expression levels of transcription factors in these animals showed a significant increase (p< 0.05) in the ratio of STAT1/STAT6on the day 21 and IRF5/IRF4on day 28 of tumor growth compared to that in untreated mice. Administration of lectin from B. subtilis IMV B-7724to mice with Ehrlich carcinoma led to the prevalence of Mph exhibiting the functional properties of M1type at late-term tumor growth. The transcription factors of the STAT and IRF signaling pathways are involved in the process of Mph polarization induced by lectin from B. subtilis IMV B-7724.