Mac the knife? Macrophages– the double-edged sword of hepatic fibrosis
J. Clin. Invest. Scott L. Friedman, et al. 115:29 doi:10.1172/JCI23928 [Go to this article.]

Figure 2
The double-edged sword of hepatic macrophage activity in hepatic fibrosis progression versus recovery. The findings by Duffield et al. (4) in this issue of the JCI suggest that hepatic macrophages may induce divergent effects on liver fibrosis by promoting stellate cell activation in the face of continued injury and fibrosis; and stellate cell apoptosis during recovery associated with fibrosis regression as injury subsides. Evidence from other studies implicates TGF-β1 as one potential paracrine stimulator of stellate cell activation by macrophages, while TRAIL may mediate stellate cell apoptosis during fibrosis regression associated with recovery. Apoptosis associated with the loss of TIMP-1 may unmask latent matrix protease activity released by either macrophages, stellate cells, or other cell types. It is not certain if the same macrophages account for the divergent activities of this cell type or whether different macrophage subsets mediate these opposing pathways.