The role and mechanisms of macrophage polarization and hepatocyte pyroptosis in acute liver failure

Front Immunol. 2023 Oct 26:14:1279264. doi: 10.3389/fimmu.2023.1279264. eCollection 2023.

Abstract

Acute liver failure (ALF) is a severe liver disease caused by disruptions in the body's immune microenvironment. In the early stages of ALF, Kupffer cells (KCs) become depleted and recruit monocytes derived from the bone marrow or abdomen to replace the depleted macrophages entering the liver. These monocytes differentiate into mature macrophages, which are activated in the immune microenvironment of the liver and polarized to perform various functions. Macrophage polarization can occur in two directions: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages. Controlling the ratio and direction of M1 and M2 in ALF can help reduce liver injury. However, the liver damage caused by pyroptosis should not be underestimated, as it is a caspase-dependent form of cell death. Inhibiting pyroptosis has been shown to effectively reduce liver damage induced by ALF. Furthermore, macrophage polarization and pyroptosis share common binding sites, signaling pathways, and outcomes. In the review, we describe the role of macrophage polarization and pyroptosis in the pathogenesis of ALF. Additionally, we preliminarily explore the relationship between macrophage polarization and pyroptosis, as well as their effects on ALF.

Keywords: acute liver failure (ALF); immune; macrophage; polarization; pyroptosis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hepatocytes / metabolism
  • Humans
  • Kupffer Cells
  • Liver Failure, Acute* / pathology
  • Macrophages
  • Pyroptosis*

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (81803884), Plan on enhancing scientific research in GMU (02-410-2302092XM), 2022 Guangzhou Medical University discipline construction projects (02-410-2206013), the 2022 Student Innovation Capacity Enhancement Program Project of Guangzhou Medical University (02-408-2304-19064XM), 2023 City school (college) enterprise joint funding projects (2023A03J0421), the Undergraduate Capacity Enhancement Innovation Project of Guangzhou Medical University (2022JXA003), the 2023 Artificial Liver Special Fund (iGandanF-1082023-RGG023), the Key Medical Discipline of Guangzhou [2021-2023] and the Key Laboratory of Guangdong Higher Education Institutes (2021KSYS009).