Influence of humoral immunoreaction on hepatic nonparenchymal cells in ex situ xenoperfused rat livers

Background. The influence of xenogeneic humoral immunoreaction on hepatic n onparenchymal cells (NPCs) was evaluated ex situ in xenoperfused rat livers . Methods. Isolated rat livers were perfused via the portal vein (PV) for 240 min. The perfusates consisted of fresh rat blood (group 1), fresh human bl ood (group 2), and fresh human blood containing 5 mug/mL soluble complement receptor type 1 (Group 3). Results. Deposition of human IgM and C5b-9 complement was observed in group 2, although only human IgM deposition was detected in group 3. Portal vein pressure in group 2 rose drastically during the first 10 min. Creatine kin ase BB component gradually increased in all groups, followed by an elevatio n in alanine aminotransferase and both parameters were significantly higher in group 2 than in groups 1 and 3. In group 2, platelet thrombi in the per ipheral PVs and periportal hemorrhage were observed after 10 min, and massi ve necrosis around the central veins after 240 min; these changes were not observed in group 1 or 3. Production of tumor necrosis factor alpha and alp ha interferon and expression of intercellular adhesion molecule 1 (ICAM-1) were lower in group 2 than in groups 1 and 3. In group 2, there were negati ve areas for ICAM-1 and tumor necrosis factor a staining around the central veins after 240 min, which were consistent with necrotic areas. Conclusions. In xenoperfused rat livers, humoral mediators initially caused the disturbance of microcirculation, which would induce long ischemia in t he pericentral areas, resulting in massive necrosis. NPC necrosis may be re sponsible for less production of cytokines and adhesion molecules in the xe noperfused livers. (C) 2001 Academic Press.