The In Vitro M1/M2 Polarization of Macrophages of BCG-Infected Mice

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Bulletin of Experimental Biology and Medicine, Vol. 169, No. 4, August, 2020 MICROBIOLOGY AND IMMUNOLOGY

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The In Vitro M1/M2 Polarization of Macrophages of BCG-Infected Mice D. A. Il’in1 and V. A. Shkurupy1,2

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 4, pp. 449-451, April, 2020 Original article submitted January 24, 2020 Cultured peritoneal macrophages from intact (control) and BCG-infected (experiment) male BALB/c mice were studied 90 days after infection. Polarization of macrophages by M1 (expression of GM-CSF, IFNg, and CD16/32) and M2 (expression of bFGF and CD36) differentiation pathways was studied with consideration for their the nuclearity class. Mononuclear cells predominated (90% and higher) in macrophage cultures of both groups and presumably, were presented by mainly epithelioid cells. The results indicated polarization of mononuclear and multinuclear macrophages in the M2 direction under conditions of BCG granulomatosis and a higher initial M2 polarization of binuclear macrophages. In control cultures, the ratio of M2 to M1 macrophages was 0.57, in experimental cultures this ratio was 1.6. It seems that long persistence of Mycobacterium tuberculosis in macrophages served as a factor stimulating the plastic processes and transformation of macrophages into epithelioid cells that form the “core” of granulomas and their enlargement upon incorporation of macrophages. Key Words: BCG vaccine Mycobacteria; macrophages; M1/M2 polarization of macrophages Granulomatosis (granulomatous inflammation) is a structural manifestation of ~70 nosologies. The debut of some of these diseases is not associated with destructive processes which initiate inflammation, and hence, it seems that these diseases should be referred to granulomatoses, but not to granulomatous inflammation [3]. The factors initiating the formation of macrophage granulomas are lysosomotropic — not biodegradable (silica, asbestos, etc.) or slowly degraded (M. tuberculosis, Candida fungi, etc.) [3]. The duration of persistence of lysosomotropic factors of different nature in macrophages (MP) determines the same nonspecific reaction of MP to these factors: hypertrophy and transformation of MP into epithelioid cells (EC) [3,6], formation of MP granulomas and their enlargement to a critical size [5] when they have no microcirculatory structures [6]. This impairs diffusion of nutrients, thus increasing the risk of spontaneous Research Institute of Experimental and Clinical Medicine, Federal Research Center of Fundamental and Translation Medicine; 2Novosibirsk State Medical University, Ministry of Health of Russia, Novosibirsk, Russia. Address for correspondence: ilindenis.ilin@yandex. ru. D. A. Il’in 1

necroses of granulomas. As a result, MP in granulomas with polypotent functions become objects and participants of destructive processes, after which granulomatosis acquires the characteristics of a granulomatous inflammation. For this reason, two phenotypes of MP, differing by their function, are distinguished: pr