The Target Cells of Injected Type I Interferons in Mouse Liver

ABSTRACT Type I interferons (IFNs) have been used for the treatment of viral hepatitis, but it is unclear which cells in the liver are affected by injected IFN. The effects of IFN have been studied by the production of 2′,5′-oligoadenylate synthetase (2′5′OAS), an IFN-inducible enzyme. Here, we studied the distribution of 2′5′OAS in mouse liver after injection of natural mouse IFN-α/β by Western blotting and immunohistochemistry using a monoclonal antibody specific to mouse 42-kDa 2′5′OAS. Injection of IFN-α/β increased the levels of liver 2′5′OAS and enhanced the intensities of immunohistochemical staining for this enzyme in both hepatocytes and Kupffer cells. In IFN-untreated normal mice, hepatocytes were lightly stained, but some of the Kupffer cells showed rather strong staining. The 2′5′OAS-positive Kupffer cells comprised ∼60% of those in normal liver, whereas this increased to ∼90% following IFN-α/β injection. Thus, hepatocytes and Kupffer cells were the targets of iniected IFN.