Macrophage Phenotype in Liver Injury and Repair

Abstract

Macrophages hold a critical position in the pathogenesis of liver injury and repair, in which their infiltrations is regarded as a main feature for both acute and chronic liver diseases. It is noted that, based on the distinct phenotypes and origins, hepatic macrophages are capable of clearing pathogens, promoting/or inhibiting liver inflammation, while regulating liver fibrosis and fibrolysis through interplaying with hepatocytes and hepatic stellate cells (HSC) via releasing different types of pro-or anti-inflammatory cytokines and growth factors. Macrophages are typically categorized into M1 or M2 phenotypes by adapting to local microenvironment during the progression of liver injury. In most occasions, M1 macrophages play a pro-inflammatory role in liver injury, while M2 macrophages exert an anti-inflammatory or pro-fibrotic role during liver repair and fibrosis. In this review, we focused on the up-to-date information about the phenotypic and functional plasticity of the macrophages and discussed the detailed mechanisms through which the phenotypes and functions of macrophages are regulated in different stages of liver injury and repair. Moreover, their roles in determining the fate of liver diseases were also summarized. Finally, the macrophage-targeted therapies against liver diseases were also be evaluated.

Ursolic acid ameliorates CCl4‐induced liver fibrosis through the NOXs/ROS pathway

“…HCs and KCs also play an important role in liver fibrosis. Damaged HCs or activated KCs can secrete TGF‐β1, one of the strongest pro‐fibrosis factors, and accelerate the activation of HSCs (Jiang et al, ; Sun et al, ). It was shown that NOX1, NOX2, NOX4 were expressed in HCs and HSCs, whereas only NOX2 was expressed in KCs.…”

Myeloid HO-1 modulates macrophage polarization and protects against ischemia-reperfusion injury

“…We then tested whether HO-1 deletion would affect macrophage polarization in vivo in a model of warm liver IRI, where macrophage phenotypes play a critical role in the degree of tissue damage and repair (10). Groups of mHO-1-KO and control mice were subjected to partial (75%) warm hepatic IRI for 90 minutes.…”

“…Classically activated macrophages (M1) are proinflammatory, while alternatively activated macrophages (M2) harbor an antiinflammatory phenotype, often after upregulation of HO-1 (8,9). Increasing evidence supports the importance of M1/M2 polarization in tissue injury and repair in liver (10), heart (11), and kidney (12). In addition, it has been reported that resolvin D1 (13) and microRNA-155 deficiency (14) ameliorate liver IRI by inducing M2 polarization.…”

Regulation of Hepatic Inflammation via Macrophage Cell Death

“…28,29 Diverse macrophage populations, based on their transcriptional profile and functions, have been observed in liver. 1,30,31 For example, restorative macrophages present after CCl 4induced liver injury have antifibrotic properties 25 and different gene signatures than restorative macrophages present after acetaminophen (APAP)-induced liver injury. [32][33][34] Several studies have also addressed the time course of hepatic macrophage changes in response to liver injury.…”