Background: The role of Kupffer cells in a hepatic xenograft rejection is still unclear. We investigated the effect of blocking Kupffer cells on xenogeneic humoral injury using rat livers as the xenoperfusion models.
Methods: Rat livers were perfused with fresh human blood after pretreatment either with normal saline (group 1; n = 8) or with gadolinium chloride (GdCl3) solution (group 2; n = 8). Tissue injury was evaluated by alanine aminotransferase release and histological examination. Tumor necrosis factor-alpha (TNF-alpha) production from rat livers was measured by enzyme-linked immunosorbent assay and also examined by immunohistochemistry. In addition, Kupffer cells were isolated after pretreatment either with normal saline or with GdCl3 solution and incubated with human serum. Localization of human C3 and IgM was examined by immunofluorescence.
Results: Alanine aminotransferase release in group 2 was significantly higher than in group 1 (P = 0.015). Histological examination revealed more severe tissue injury in group 2. The mean TNF-alpha level was not significantly different between the two groups. In immunohistochemistry, TNF-alpha was positive primarily on vascular endothelial cells in both groups. Immunofluorescence of saline-treated Kupffer cells showed an uptake of human C3 in the cytoplasm, whereas no uptake was observed in GdCl3-treated cells. The uptake of human IgM did not differ between the two groups.
Conclusions: These results suggest that Kupffer cells have a protective role in preventing xenogeneic humoral injury. Their ability to absorb xenogeneic complements may contribute to this protective mechanism.