HYPERACUTE REJECTION OF LIVER ALLOGRAFTS IN SENSITIZED RATS - ROLE OFNONPARENCHYMAL LIVER-CELLS

Reasons why liver allografts are more resistant to antibody mediated r ejection than other organ allografts are not fully understood. In orde r to define the role of nonparenchymal liver cells, we have compared t he fate of liver allografts in two combinations of sensitized inbred r ats. In the DA into LEW combination, hyperacute rejection of liver all ografts was observed (mean survival time of liver grafted rats was 5.2 +/- 0.6 hr). A sharp decrease of the level of cytotoxic antibodies wa s 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 re jection 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 cel lular rejection. A decrease in the level of cytotoxic antibodies was p resent and deposits of IgG, IgM, C3, and fibrinogen were more signific ant. 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 suggesti ve of antibody-mediated rejection and deposits of IgG, IgM, and C3 wer e reduced. The results suggest the hypotesis that resistance of liver allografts to antibody-mediated rejection is probably due to the abili ty of nonparenchymal liver cells to absorb preformed cytotoxic antibod ies and complement. (C) 1995 Academic Press, Inc.