Enhanced hepatocyte growth factor expression associated with prolonged rathepatic 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 surv ival of hepatic allografts from ACI(RT1(a)) to LEW(RT1(1)) rats. We investi gated hepatocyte growth factor (HGF) expression in rat hepatic allografts o f recipients pretreated with or without DST. Methods. The levels of HGF mRNA and protein in hepatic allografts were dete rmined after transplantation. The localization of HGF(+) cells was identifi ed with a rat anti-HGF monoclonal antibody. Results. Plasma HGF concentrations in transplanted rats treated with DST we re significantly and persistently increased compared to untreated rats with hepatic allografts. The number of HGF(+) cells in hepatic allografts of re cipients pretreated with DST on day 14 was significantly greater than that in allografts of untreated recipients on day 7. HGF(+) cells were also foun d in the marginal zone and red pulp of recipient spleens. Northern blot ana lysis 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 b oth DST-treated and untreated recipient spleens. Conclusions. Enhanced HGF expression in rat hepatic allografts is associate d with immunologic unresponsiveness induced by DST.