A. Pascher et al., IMMUNOPATHOLOGICAL OBSERVATIONS AFTER XENOGENEIC LIVER PERFUSIONS USING DONOR PIGS TRANSGENIC FOR HUMAN DECAY-ACCELERATING FACTOR, Transplantation, 64(3), 1997, pp. 384-391
Background, Donor pigs transgenic for human decay-accelerating factor
(hDAF) were used in a xenogeneic ex vivo liver perfusion model to stud
y the effect of this modification on the development of hyperacute rej
ection, Methods. Three transgenic pigs were hepatectomized after hypot
hermic portal and transaortal gravity perfusion, Livers from six nontr
ansgenic pigs served as controls, All livers were perfused for 3 hr wi
th human blood from two donors diluted to a hematocrit of 30%, Particu
lar importance was placed on the use of an optimal perfusion technique
incorporating the floating suspension of the organs in a waterbath an
d intermittent external pressurization. Biochemical, physiological, an
d immunological parameters were assessed. Tissue specimens taken befor
e and after perfusion were analyzed using routine histology, electron
microscopy, and immunohistology, Results, Complement activation was mo
re pronounced in the control group, AP50 and CH50 values fell to about
60% of the initial levels in control experiments, whereas they remain
ed at 80% of the initial levels during perfusion of hDAF livers, After
180 min, pig tumor necrosis factor a levels were 7862+/-1645 pg/ml fo
r unmodified livers and 2830+/-734 pg/ml in the hDAF group, Human tumo
r necrosis factor alpha levels were similar in both groups, Control li
vers showed marked morphological alterations and distinct deposition o
f complement factors, whereas livers expressing hDAF showed no signs o
f hepatocellular necrosis and almost no complement deposition beyond C
3 activation. Conclusions, These results confirm that the transgenic e
xpression of the human complement regulatory protein hDAF reduces comp
lement activation and prevents hyperacute rejection in a xenogeneic li
ver perfusion model over the 3-hr evaluation period used in this study
.