Promotion of macrophage activation and inflammation in chronic liver disease by the histidine-rich glycoprotein

Danger signals and cytokines released by immune cells influence the functional differentiation of macrophages in chronic inflammation. Recently, the liver-derived plasma protein histidine-rich glycoprotein (HRG) was demonstrated to mediate the transition of alternatively activated (M2) to pro-inflammatory and anti-tumoral (M1) macrophages. We hypothesized that liver-derived HRG is a critical mediator of hepatic macrophage functionality and therefore studied its role in chronic liver disease using mouse models of hepatic fibrosis in Hrg-/- and wildtype (WT) mice. In steady state, hepatic macrophages were reduced…