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Abstract <p><b>Objective:</b> The relevance of studying the role of macrophages and their multinucleated forms in the pathogenesis of tuberculous granulomatosis is determined by its widespread prevalence, severe socio-economic consequences and necrotic complications, which are based on the high destructive potential of macrophages associated with hydrolases involved in the degradation of extracellular matrix components. The purpose of the study was to investigate the implementation of multinucleation, apoptosis and expression of hydrolases in macrophages of BCG-infected mice. <b>Material and methods:</b> Macrophage multinucleation, apoptosis and expression of matrix metalloproteinases (MMP-1, MMP-9), cathepsins (CatB, CatD), caspase-3, and p53 protein were studied. in peritoneal cell cultures established from intact and BCG-infected BALB/c mice. <b>Results:</b> The number of multinucleated macrophages increased in time. It reached the maximum value at 3 months of observation, but after 2 months it had almost his level. The implementation of apoptosis, and multinucleation in macrophages had a complex pattern , determining the composition of their subpopulations. The dynamics of expression of the studied hydrolases in macrophages indicated their unequal role in tissue necrosis at different stages of granulomatogenesis. It has been shown multinucleated macrophages exhibit high functional capacity to produce hydrolases of certain types. Intensive expression of MMP-1 was registered in the early stages of granulomatogenesis; its maximum value as well as expression of CatD were reached at 3 months, and pronounced expression of MMP-9 was observed at 6 months. <b>Conclusion:</b> Stimulation of plasticity processes in macrophages under conditions of BCG granulomatosis induces the formation of multinuclear macrophages with high functional potential and intensive expression of hydrolases at 2 and 3 months of granulogenesis. These are periods of high risk of necrotic complications of tuberculous granulomatosis, which should be taken into account when developing methods for their prevention and therapeutic correction.</p>

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Multinucleation and Apoptosis of Macrophages in BCG-Infected Mice and Production of Cathepsins and Matrix Metalloproteinases in These Cells

  • 期刊论文

  • 发表日期：

    2025年1月20日

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  • D. A. Il’in

摘要

Abstract

Objective: The relevance of studying the role of macrophages and their multinucleated forms in the pathogenesis of tuberculous granulomatosis is determined by its widespread prevalence, severe socio-economic consequences and necrotic complications, which are based on the high destructive potential of macrophages associated with hydrolases involved in the degradation of extracellular matrix components. The purpose of the study was to investigate the implementation of multinucleation, apoptosis and expression of hydrolases in macrophages of BCG-infected mice. Material and methods: Macrophage multinucleation, apoptosis and expression of matrix metalloproteinases (MMP-1, MMP-9), cathepsins (CatB, CatD), caspase-3, and p53 protein were studied. in peritoneal cell cultures established from intact and BCG-infected BALB/c mice. Results: The number of multinucleated macrophages increased in time. It reached the maximum value at 3 months of observation, but after 2 months it had almost his level. The implementation of apoptosis, and multinucleation in macrophages had a complex pattern , determining the composition of their subpopulations. The dynamics of expression of the studied hydrolases in macrophages indicated their unequal role in tissue necrosis at different stages of granulomatogenesis. It has been shown multinucleated macrophages exhibit high functional capacity to produce hydrolases of certain types. Intensive expression of MMP-1 was registered in the early stages of granulomatogenesis; its maximum value as well as expression of CatD were reached at 3 months, and pronounced expression of MMP-9 was observed at 6 months. Conclusion: Stimulation of plasticity processes in macrophages under conditions of BCG granulomatosis induces the formation of multinuclear macrophages with high functional potential and intensive expression of hydrolases at 2 and 3 months of granulogenesis. These are periods of high risk of necrotic complications of tuberculous granulomatosis, which should be taken into account when developing methods for their prevention and therapeutic correction.