Hepatic Macrophages in Liver Injury

Abstract

Ample evidence suggests that hepatic macrophages play key roles in the injury and repair mechanisms during liver disease progression. There are two major populations of hepatic macrophages: the liver resident Kupffer cells and the monocyte-derived macrophages, which rapidly infiltrate the liver during injury. Under different disease conditions, the tissue microenvironmental cues of the liver critically influence the phenotypes and functions of hepatic macrophages. Furthermore, hepatic macrophages interact with multiple cells types in the liver, such as hepatocytes, neutrophils, endothelial cells, and platelets. These crosstalk interactions are of paramount importance in regulating the extents of liver injury, repair, and ultimately liver disease progression. In this review, we summarize the novel findings highlighting the impact of injury-induced microenvironmental signals that determine the phenotype and function of hepatic macrophages. Moreover, we discuss the role of hepatic macrophages in homeostasis and pathological conditions through crosstalk interactions with other cells of the liver.

In Vivo and In Vitro Characterization of Primary Human Liver Macrophages and Their Inflammatory State

“…This lobule-specific pattern was observable either pericentral (D04), periportal (D05), or both (D13), but was also randomly distributed over the whole tissue section (D08). It was demonstrated in a mouse model that a pericentral accumulation of LMs can be a specific feature of CCA [ 36 ], similar to our observation of the pro-inflammatory macrophage distribution in a patient with iCCA (D04). The periportal concentration and ring-like appearance of the CD80+ cells on the lobule borders found in the tissue of D05 with diagnosed HCC could indicate a defined area of injury formed by MDMs as described elsewhere [ 7 ].…”

Regeneration Defects in Yap and Taz Mutant Mouse Livers Are Caused by Bile Duct Disruption and Cholestasis

“…Necrotic cell corpses are mainly removed by macrophages. 30 In wild-type mice, the number of resident macrophages (Kupffer cells [KCs]; F4/80 hi CD11b int ) declined during the initial phase after CCl 4 , but then reappeared and accumulated around the regenerating regions at 72 hours after CCl 4 (Figure 5A-D and Supplementary Figure 19A). 31 This reappearance of KCs was preceded by a dramatic influx of infiltrating monocytes (F4/80 int CD11b hi Ly6C hi ) at 48 hours after CCl 4 (Figure 5E and Supplementary Figure 19B), which probably produced at least some of the newly emerging macrophages at 72 hours.…”

Role of MIF in coordinated expression of hepatic chemokines in patients with alcohol-associated hepatitis

“…The current study highlights critical changes in expression of chemokines in the livers of patients with AH and how changes in expression of multiple chemokines might be controlled in patients with severe AH. Canonical functions of chemokines and MIF in ALD are associated with leukocyte infiltration into the liver, including monocytes, macrophages, and neutrophils ( 23 – 25 ). There is some controversy to what roles leukocytes play in the progression of ALD in humans; the accumulation of neutrophils in the livers of patients with AH has been associated with both favorable and negative outcomes for patient morbidity and mortality ( 25 – 28 ).…”