Immunohistochemical detection of myeloperoxidase and its oxidation products in Kupffer cells of human liver

Oxidative damage to tissue proteins has been implicated in the pathogenesis of liver disease, but the mechanisms that promote oxidation in vivo are un clear. Hydrogen peroxide is transformed into an array of potentially damagi ng reactants by the heme protein myeloperoxidase. This proinflammatory enzy me is expressed by circulating neutrophils and monocytes but is generally t hought to be absent from tissue macrophages. To determine whether myelopero xidase is present in Kupffer cells, the fixed-tissue macrophages of liver, Western blot analysis, and immunohistochemistry were performed. Two differe nt antibodies monospecific for myeloperoxidase Identified a 60-kd protein, the predicted molecular mass of myeloperoxidase, in human liver extracts. I mmunostaining detected the enzyme in sinusoidal lining cells of normal and diseased human livers. Immunofluorescence confacal microscopy demonstrated co-localization of myeloperoxidase and CD68, a monocyte/macrophage marker, in sinusoidal lining cells. Numerous myeloperoxidase-expressing cells were also evident in the fibrous septa of cirrhotic livers. Immunostaining with an antibody to proteins modified by hypochlorous, acid, a characteristic pr oduct of the enzyme, indicated that myeloperoxidase is enzymatically active in cases of acute liver injury and cirrhosis. These findings identify myel operoxidase as a component of human Kupffer cells. Oxidative damage resulti ng from the action of myeloperoxidase may contribute to acute liver injury and hepatic fibrogenesis.