Macrophages in necrotic liver lesion repair: opportunities for therapeutical applications

Abstract

Healthy livers contain 80% of body resident macrophages known as Kupffer cells. In diseased livers, the number of Kupffer cells usually drops, but is compensated by infiltration of monocyte-derived macrophages, which can differentiate into Kupffer-like cells. Early studies suggest that Kupffer cells play important roles in both promoting liver injury as well as liver regeneration. Yet, the distinction of the functionalities from resident and infiltrating macrophages is not always made. By using more specific macrophage markers and targeted cell depletion and single cell RNA sequencing, recent studies revealed several subsets of monocyte-derived macrophages that play important functions in inducing liver damage and inflammation as well as in liver repair and regeneration. In this review, we discuss the different roles that hepatic macrophages play in promoting necrotic liver lesion resolution and dead cell clearance, as well as the targeting of these cells as potential tools for the development of novel therapies for acute liver failure and acute-on-chronic liver failure.

Necrotic Liver Lesion Resolution: Another Mode of Liver Regeneration

“…Macrophages, at all stages: By using more specific macrophage markers and with the help of advanced tools, several subsets of macrophages are emphasized to play important functions in liver injury repair and regeneration. 53 Meanwhile, MoMFs are rapidly recruited and localized to the border of liver necrotic areas at the early stage of the ConA-mediated acute liver injury and subsequently work with hepatic stellate cells (HSCs) to remove necrotic tissue and cavities at the later stage (approximately after 72 to 96 hours post-ConA injection). 9,51,53 Instead of liver resident macrophages Kupffer cells, MoMFs (IBA1 + CLEC4F -) aggregated and encapsulated the necrotic lesions to form a 'ring-like' structure, containing two particularly clusters: C1q + and Pdgfb + MoMFs, which play key roles in removing dead cells and activating HSCs, respectively.…”

“…53 Meanwhile, MoMFs are rapidly recruited and localized to the border of liver necrotic areas at the early stage of the ConA-mediated acute liver injury and subsequently work with hepatic stellate cells (HSCs) to remove necrotic tissue and cavities at the later stage (approximately after 72 to 96 hours post-ConA injection). 9,51,53 Instead of liver resident macrophages Kupffer cells, MoMFs (IBA1 + CLEC4F -) aggregated and encapsulated the necrotic lesions to form a 'ring-like' structure, containing two particularly clusters: C1q + and Pdgfb + MoMFs, which play key roles in removing dead cells and activating HSCs, respectively. Complement component C1q elicits macrophage phenotype tailored specifically for clearance of apoptotic cells.…”