Involvement of ICAM-1/LFA-1 adhesion molecule set in rat orthotopic liver transplantation
Omura, T.
Hokkaido Journal of Medical Science 69(5): 1220-1231
1994
ISSN/ISBN: 0367-6102 PMID: 7868060 Document Number: 428584
The distribution of ICAM-1/LFA-1-positive cells in rat liver grafts was investigated. The effect on graft survival of graft perfusion with anti-ICAM-1 monoclonal antibody before transplantation was also examined. Using ACI (RT-1av1) and LEW (RT-1(1)) inbred rats, orthotopic liver transplantation was performed both in allogeneic (ACI to LEW) and syngeneic (ACI to ACI) combinations. Transplanted liver tissues on days 2, 4 and 7 were immunohistochemically stained, using mouse anti-rat ICAM-1 monoclonal antibody (1A29, IgG1) and mouse anti-rat LFA-1 monoclonal antibody (WT-1, IgG2a). ACI livers perfused via portal vein with either 1A29, control antibody or lactate-Ringer's solution were transplanted to LEW recipients. ICAM-1 expression in normal ACI livers was confined to the endothelium of large portal vein and some central veins. A weak ICAM-1 expression was also observed on some sinusoidal endothelium. A small number of LFA-1-positive cells were resided in the normal liver. In allografted ACI livers, an intense ICAM-1 expression was induced on sinusoidal endothelium within 2 days after transplantation, and its expression was further increased on days 4 and 7. ICAM-1 expression on hepatocytes was also induced. LFA-1 positive infiltrates were gradually increased in number during the course of rejection, especially in the sinusoidal area. In the syngeneic combination, only a slight ICAM-1 induction on sinusoidal endothelium was observed. ICAM-1 upregulation on target structures of liver graft rejection suggests the importance of ICAM-1/LFA-1 in the pathogenesis of allograft rejection. Liver grafts perfused with anti-ICAM-1 monoclonal antibody were destroyed more rapidly than those perfused with control antibody or lactate-Ringer's solution both in allogeneic and syngeneic combinations. Histological examination revealed spotty ischemic necrosis in grafted liver. Perfusion with the antibody might cause the circulatory disturbance probably through the mechanism differing from alloantigen-specific response.