Enhanced hepatocyte growth factor expression associated with prolonged rat hepatic allograft survival in recipients pretreated with donor-specific blood

Background. Pretransplantation injection of freshly heparinized donor blood (donor-specific blood transfusion, or DST) significantly prolongs the survival of hepatic allografts from ACI(RT1 a ) to LEW(RT1 1 ) rats. We investigated hepatocyte growth factor (HGF) expression in rat hepatic allografts of recipients pretreated with or without DST. Methods. The levels of HGF mRNA and protein in hepatic allografts were determined after transplantation. The localization of HGF + cells was identified with a rat anti-HGF monoclonal antibody. Results. Plasma HGF concentrations in transplanted rats treated with DST were significantly and persistently increased compared to untreated rats with hepatic allografts. The number of HGF + cells in hepatic allografts of recipients pretreated with DST on day 14 was significantly greater than that in allografts of untreated recipients on day 7. HGF + cells were also found in the marginal zone and red pulp of recipient spleens. Northern blot analysis revealed the presence of three HGF + cell phenotypes: HGF + ED1 + , HGF + ED2 + , and HGF + ED1 - ED2 - . Most HGF + cells were ED1 - ED2 - . In situ hybridization demonstrated HGF mRNA in the mononuclear cells in the portal and sinusoidal areas as well as the marginal zone and red pulp in both DST-treated and untreated recipient spleens. Conclusions. Enhanced HGF expression in rat hepatic allografts is associated with immunologic unresponsiveness induced by DST.