Hyperacute Rejection of Liver Allografts in Sensitized Rats: Role of Nonparenchymal Liver Cells

Abstract

Reasons why liver allografts are more resistant to antibody mediated rejection than other organ allografts are not fully understood. In order to define the role of nonparenchymal liver cells, we have compared the fate of liver allografts in two combinations of sensitized inbred rats. In the DA into LEW combination, hyperacute rejection of liver allografts was observed (mean survival time of liver grafted rats was 5.2 ± 0.6 hr). A sharp decrease of the level of cytotoxic antibodies was observed after transplantation associated with deposits of IgG, IgM, C3, and fibrinogen on sinusoidal cells. Macroscopic and histological aspects of liver allografts were suggestive of an antibody-mediated rejection with congestion and portal hemorrhage. On the contrary, in the LEW into BN combination, survival time was significantly longer (259.2 ± 25.2 hr), whereas histological studies demonstrated signs of cellular rejection. A decrease in the level of cytotoxic antibodies was present and deposits of IgG, IgM, C3, and fibrinogen were more significant. After blockade of the Kupffer cells of the LEW-transplanted liver, survival time of the BN rats was significantly reduced (38.8 ± 8.0 hr). Macroscopic and histological aspects of the grafts were suggestive of antibody-mediated rejection and deposits of IgG, IgM, and C3 were reduced. The results suggest the hypotesis that resistance of liver allografts to antibody-mediated rejection is probably due to the ability of nonparenchymal liver cells to absorb preformed cytotoxic antibodies and complement.