Nalan KAYA TEKTEMUR, Dürrin Özlem DABAK, Nida ÇAYLAN, Neriman ÇOLAKOĞLU

M1/M2 Liver Macrophage Polarization After Antigenic Stimulation with Lipopolysaccharide (LPS) in Rats

Objective: In our study, we aimed to detect M1/M2 macrophage polarization in rat liver tissue by immunohistochemical staining after antigenic stimulation with lipopolysaccharide (LPS). Materials and Methods: Twenty-four Spraque-Dawley male 10-week-old rats were used in the study. Rats were randomly divided into 4 groups (n=6): Control-24 group, Control-48 group, LPS- 24 group and LPS-48 group. Rats in the control groups were administered 1 mL of saline intraperitoneally (i.p) and the animals were decapitated after 24 or 48 hours. The rats in the LPS groups were administered with 5 mg/kg LPS (in 1 mL saline) i.p. After 24 or 48 hours, the rats were decapitated and the study was terminated. Results: Inflammatory cell infiltration and hyperemia were detected in liver tissues of rats in LPS- 24 and LPS-48 groups as a result of examination of sections stained with hematoxylin-eosin (H&E). Sinusoidal dilatation was also noted in the LPS-24 group. CD68 immunoreactivity was found to be significantly increased in LPS-treated rat liver sections when compared to control groups (P

PDF

___

1. Varol C, Mildner A, Jung S. Macrophages: Development and tissue specialization. Annu Rev Immunol 2015; 33: 643-675.
2. Ju C, Tacke F. Hepatic macrophages in homeostasis and liver diseases: From pathogenesis to novel therapeutic strategies. Cellular and Molecular Immunology 2016; 13: 316-327.
3. Tacke F. Targeting hepatic macrophages to treat liver diseases. J Hepatol 2017; 66: 1300-1312.
4. Yamate J, Izawa T, Kuwamura M. Histopathological Analysis of Rat Hepatotoxicity Based on Macrophage Functions: in Particular, an Analysis for Thioacetamide- induced Hepatic Lesions. Food Safety 2016; 4: 61-73.
5. Murray PJ. Macrophage polarization. Ann Rev Physiol 2017; 79: 541-566.
6. Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: Time for reassessment. F1000 Prime Reports 2014; 6: 13.
7. Seemann S, Zohles F, Lupp A. Comprehensive comparison of three different animal models for systemic İnflammation. J Biomed Sci 2017; 24: 60.
8. Tektemur A, Ozaydin S, Onalan EE, et al. TRPM2 mediates distruption of autophagy machinery and correlates with the grade level in prostate cancer. J Cancer Res Clin Oncol 2019; 145: 1297-1311.
9. Wen Y, Lambrecht J, Ju C, Tacke F. Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities. Cellular & Molecular Immunology 2021; 18: 45-56.
10. Law SK, Micklem KJ, Shaw JM, et al. A new macrophage differentiation antigen which is a member of the scavenger receptor superfamily. Eur J Immunol 1993; 23: 2320-2325.
11. Kristiansen M, Graversen JH, Jacobsen C, et al. Identification of haemoglobulin scavenger receptor. Nature 2001; 409: 198-201.
12. Martinez FO, Sica A, Mantovani A, Locati M. Macrophage activation and polarization. Front Biosci 2008; 13: 453- 461.
13. Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 2002; 23: 549- 555.
14. Duffield JS, Forbes SJ, Constandinou CM, et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest 2005; 115: 56- 65.
15. Tacke F. Targeting hepatic macrophages to treat liver diseases. J Hepatol 2017; 66: 1300-1312.
16. Yamate J, Izawa T, Kuwamura M. Histopathological analysis of rat hepatotoxicity based on macrophage functions: In particular, an analysis for thioacetamide- induced hepatic lesions. Food Safety 2016; 4: 61-73.
17. Ustaçelebi Ş. Temel ve Klinik Mikrobiyoloji. Ankara: Güneş Kitabevi, 1999.
18. Hamano T, Tong V, Mutai M, Hayashi M, Tanaka E. Kupffer cell-mediated cytotoxicity induced by lipopolysaccharide 0111:B4 is greater in dogs than in rats and monkeys. J Toxicol Sci Feb 2002; 27: 1-9.
19. Harris RL, Musher DM, Bloom K, et al. Manifestations of sepsis. Arch Intern Med 1987; 147: 1895–1906.
20. Lichtman SN, Wang J, Lemasters JJ. Lipopolysaccharide- stimulated TNF-alpha release from cultured rat Kupffer cells: Sequence of intracellular signaling pathways. J Leukoc Biol 1998; 64: 368-372.
21. Chensue SW, Terebuh PD, Remick DG, Scales WE, Kunkel SL. In vivo biologic and immunohistochemical analysis of interleukin-1 alpha, beta and tumor necrosis factor during experimental endotoxemia. Kinetics, Kupffer cell expression, and glucocorticoid effects. Am J Pathol 1991; 138: 395-402
22. Krieg AM. Therapeutic potential of toll-like receptor 9 activation, Nature Reviews Drug Discovery 2006; 5; 6: 471-484.
23. McDonald B, Jenne CN, Zhuo L, Kimata K, Kubes P. Kupffer cells and activation of endothelial TLR4 coordinate neutrophil adhesion within liver sinusoids during endotoxemia. Am J Physiol Gastrointest Liver Physiol 2013; 305: 797‑806.
24. Liu Y, Li F, Zhang L, et al. Taurine alleviates lipopolysaccharide‑induced liver injury by anti‑inflammation and antioxidants in rats. Mol Med Rep 2017; 16: 6512-6517.
25. Rao AJ, Gibon E, Ma T, et al. M1 and M2 Macrophage Polarization in vitro with exposure to LPS and IL-4. Poster No.1917, Annual Meeting, ORS 2012.
26. Golbar HM, Izawa T, Yano R, et al. Immunohistochemical characterization of macrophages and myofibroblasts in α- Naphthylisothiocyanate (ANIT)-induced bile duct injury and subsequent fibrogenesis in rats. Toxicol Pathol 2011; 39: 795-808.
27. Golbar HM, Izawa T, Juniantito V, et al. Immunohistochemical characterization of macrophages and myofibroblasts in fibrotic liver lesions due to Fasciola infection in cattle. J Vet Med Sci 2013; 31: 857-865.
28. Law SK, Micklem KJ, Shaw JM, et al. A new macrophage differentiation antigen which is a member of the scavenger receptor superfamily. Eur J Immunol 1993; 23: 2320-2325.
29. Kristiansen M, Graversen JH, Jacobsen C, et al. Identification of haemoglobulin scavenger receptor. Nature 2001; 409: 198-201.
30. Hao NB, Lü MH, Fan YH, et al. Macrophages in tumor microenvironments and the progression of tumors. Clin Dev Immunol 2012; 11.
31. Sica A Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 2012; 122: 787- 795.
32. Murray PJ, Wynn TA. Obstacles and opportunities for understanding macrophage polarization. J Leukoc Biol 2011; 89: 557-563.
33. Benoit M, Desnues B, and Mege JL. Macrophage polarization in bacterial infections, The Journal of Immunology 2008; 181: 3733-3739.
34. Shaughnessy LM, Swanson JA. The role of the activated macrophage in clearing Listeria monocytogenes infection. Front Biosci. 2010; 12: 2683-2692.
35. Jouanguy E, Doffinger R, Dupuis S, et al. IL-12 and IFN- gamma in host defense against mycobacteria and salmonella in mice and men. Curr Opin Immunol 1999; 11: 346-351.
36. Seemann S, Zohles F, Lupp A. Comprehensive comparison of three different animal models for systemic İnflammation. J Biomed Sci 2017; 24: 60.