Published online Apr 28, 2020. doi: 10.3748/wjg.v26.i16.1879
Peer-review started: January 7, 2020
First decision: March 6, 2020
Revised: March 31, 2020
Accepted: April 8, 2020
Article in press: April 8, 2020
Published online: April 28, 2020
The liver functions, in part, to prevent exposure of the body to potentially harmful substances ingested in the diet. While it is highly efficient at accomplishing this, it is frequently prone to liver injury due to the biotransformation of xenobiotics into toxic metabolites. To counter this injury, the liver has evolved a unique capacity to rapidly and efficiently repair itself. Successful resolution of acute liver injury relies on hepatic macrophage populations that orchestrate the reparative response. After injury, Kupffer cells, the resident macrophages of the liver, become activated and secrete proinflammatory cytokines. These cytokines recruit other immune cells, including monocyte-derived macrophages, to the liver where they contribute to the repair process. Monocyte-derived macrophages traffic into the necrotic foci where they rapidly phagocytose dead cell debris. Simultaneous with this process, these cells change phenotype from a proinflammatory macrophage to a pro-restorative macrophage that produce pro-mitogenic growth factors and anti-inflammatory cytokines. Ultimately this process triggers resolution of inflammation, and along with proliferation of other hepatic cells, restores the liver architecture and function. While the mechanisms regulating specific macrophage functions during repair remain to be elucidated, recent studies indicate a key role for the fibrinolytic system in coordinating macrophage function during repair. In this review, we will highlight the function and role of hepatic macrophages in repair after acute liver injury, and will discuss the role of the fibrinolytic enzyme, plasmin, in regulation of these various processes.
Core tip: Macrophages contribute to repair of the liver after injury. After injury, Kupffer cells release cytokines that recruit monocyte-derived macrophages that phagocytose dead cell debris. These cells switch phenotype becoming pro-restorative macrophages that terminate cytokine synthesis and produce pro-mitogenic growth factors that facilitate liver repair.