Mannan binding lectin‐associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells

Summary Mannan binding lectin ( MBL )‐associated serine protease type 1 ( MASP ‐1) has a central role in the lectin pathway of complement activation and is required for the formation of C3 convertase. The activity of MASP ‐1 in the peripheral blood has been identified previously as a highly significant predictor of the severity of liver fibrosis in hepatitis C virus ( HCV ) infection, but not in liver disease of other aetiologies. In this study we tested the hypotheses that expression of MASP ‐1 may promote disease progression in HCV disease by direct activation of hepatic stellate cells ( HSCs ) and may additionally be up‐regulated by HCV . In order to do so, we utilized a model for the maintenance of primary human HSC in the quiescent state by culture on basement membrane substrate prior to stimulation. In comparison to controls, recombinant MASP ‐1 stimulated quiescent human HSCs to differentiate to the activated state as assessed by both morphology and up‐regulation of HSC activation markers α‐smooth muscle actin and tissue inhibitor of metalloproteinase 1. Further, the expression of MASP ‐1 was up‐regulated significantly by HCV infection in hepatocyte cell lines. These observations suggest a new role for MASP ‐1 and provide a possible mechanistic link between high levels of MASP ‐1 and the severity of disease in HCV infection. Taken together with previous clinical observations, our new findings suggest that the balance of MASP ‐1 activity may be proinflammatory and act to accelerate fibrosis progression in HCV liver disease.