M1- and M2-macrophage polarization in rat liver cirrhosis induced by thioacetamide (TAA), focusing on Iba1 and galectin-3

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• 作者：Kavindra Kumara Wijesundera¹ ; Takeshi Izawa¹ ; Anusha Hemamali Tennakoon ; Hiroshi Murakami ; Hossain M. Golbar ; Chisa Katou-Ichikawa ; Miyuu Tanaka ; Mitsuru Kuwamura ; Jyoji Yamate ; ^{yamate@vet.osakafu-u.ac.jp" class="auth_mail}
• 关键词：Thioacetamide ; Cirrhosis ; Macrophage polarization ; Iba1 ; Galectin-3
• 刊名：Experimental and Molecular Pathology
• 出版年：June 2014
• 年：2014
• 卷：96
• 期：3
• 页码：382-392
• 全文大小：2666 K

文摘

Resident and exudate macrophages play an important role in the development of liver cirrhosis. Ionized calcium binding adaptor molecule 1⁺ (Iba1⁺) and galectin-3⁺ (Gal-3⁺) macrophages regulate liver fibrosis probably through pro-inflammatory and pro-fibrotic factors. Macrophages show polarized functions in liver fibrosis; however, M1-/M2-polarization of Iba1⁺ and Gal-3⁺ macrophages remains obscured. This study investigated the M1-/M2-polarized properties of Iba1⁺ and Gal-3⁺ macrophages in chemical-induced liver cirrhosis.

Materials and methods

Cirrhosis was induced in F344 rats by repeated injections of thioacetamide (100 mg/kg BW, twice a week for 25 weeks). Liver samples were collected from post-first-injection (PFI) week 5 to 25. Macrophage immunophenotypes and myofibroblasts in the fibrous bridges (FBs) and pseudolobules (PLs) were analyzed by immunohistochemistry. Expressions of M1- and M2-related factors were analyzed with RT-PCR, separately in FBs and PLs.

Results

Activation of myofibroblasts was most pronounced in livers at week 15. CD68⁺ (M1), CD204⁺ (M2), Iba1⁺ and Gal-3⁺ macrophages in the FBs increased gradually and peaked at week 15, consistent with the upregulation of both M1-(MCP-1, IFN-纬, IL-1尾, IL-6, and TNF-伪) and M2-(TGF-尾1, IL-4, and IL-10) related factors. Iba1⁺ and Gal-3⁺ macrophages showed both M1- and M2-immunophenotypes. CD163⁺ macrophages showed a persistent increase, consistent with TGF-尾1 upregulation. MHC class II⁺ macrophages increased in the developing fibrotic lesions, and then reduced in the advanced stage cirrhosis.

Conclusion

Both M1- and M2-macrophage polarizations occur during development of liver cirrhosis. Iba1⁺ and Gal-3⁺ macrophages participate in liver cirrhosis through production of both M1- and M2-related factors.