Abstract
Different etiologies such as drug toxicity, acute viral hepatitis B, or acetaminophen poisoning can cause acute liver injury or even acute liver failure (ALF). Excessive cell death of hepatocytes in the liver is known to result in a strong hepatic inflammation. Experimental murine models of liver injury highlighted the importance of hepatic macrophages, so-called Kupffer cells, for initiating and driving this inflammatory response by releasing proinflammatory cytokines and chemokines including tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-1beta, or monocyte-chemoattractant protein-1 (MCP-1, CCL2) as well as activating other non-parenchymal liver cells, e.g., endothelial or hepatic stellate cells. Many of these proinflammatory mediators can trigger hepatocytic cell death pathways, e.g., via caspase activation, but also activate protective signaling pathways, e.g., via nuclear factor kappa B (NF-κB). Recent studies in mice demonstrated that these macrophage actions largely depend on the recruitment of monocytes into the liver, namely of the inflammatory Ly6c+ (Gr1+) monocyte subset as precursors of tissue macrophages. The chemokine receptor CCR2 and its ligand MCP-1/CCL2 promote monocyte subset infiltration upon liver injury. In contrast, the chemokine receptor CX3CR1 and its ligand fractalkine (CX3CL1) are important negative regulators of monocyte infiltration by controlling their survival and differentiation into functionally diverse macrophage subsets upon injury. The recently identified cellular and molecular pathways for monocyte subset recruitment, macrophage differentiation, and interactions with other hepatic cell types in the injured liver may therefore represent interesting novel targets for future therapeutic approaches in ALF.
Highlights
Acute liver injury (ALI) and acute liver failure (ALF) represent different severity stages of a sudden deterioration of liver function without evidence for prior chronic liver disease
Tremendous research efforts have corroborated the concept that hepatic macrophages are central in the pathogenesis of acute hepatic injury
Liver necrosis as the macroscopic sequel to extensive hepatocyte cell death can be reverted by depletion of macrophages in many experimental models
Summary
Acute liver injury (ALI) and acute liver failure (ALF) represent different severity stages of a sudden deterioration of liver function without evidence for prior chronic liver disease. It is a dreaded disease condition due to its tremendous morbidity and mortality without adequate treatment. The present review intends to focus on hepatic macrophages in ALI as well as on monocytes, the bone-marrowderived macrophage precursors that are vigorously recruited upon liver damage Chemokine pathways governing this process will be a main focus in the subsequent sections, because interference with these pathways might perspectively allow developing novel and effective therapeutic approaches for ALF in the near future
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
