Do hepatic macrophages degrade ECM during fibrosis regression?
A more compelling question is whether macrophages directly promote matrix degradation during resolution of liver fibrosis through production of matrix-degrading proteases or by stimulating either the release or activation of proteases by other cell types, including stellate cells. Identifying macrophages as the elusive source of enzymes that degrade the fibrillar interstitial (i.e., scar) matrix during fibrosis resolution would represent a major advance, although the primary substrate for the hepatic macrophage’s major known metalloproteinase, MMP-9, is basement-membrane collagen, not fibrillar collagen (21). Still, more careful characterization of recovery-associated macrophages could yield some surprises, including macrophage release of additional proteases or the existence of a more broad substrate specificity of MMP-9 that also includes fibrillar collagens; moreover, recent data suggest that activated stellate cells may also express MMP-9 (22). Finally, degradation of fibrillar ECM
