O. Ichiguchi et al., Enhanced hepatocyte growth factor expression associated with prolonged rathepatic allograft survival in recipients pretreated with donor-specific blood, TRANSPLANT, 67(1), 1999, pp. 115-123
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.