Effect of continuous complement inhibition using soluble complement receptor type 1 on survival of pig-to-primate cardiac xenografts.
A single bolus of soluble complement (C) receptor type 1 (sCR1, TP-10) has been shown to delay hyperacute rejection (HAR) of porcine cardiac xenografts (Xgs) by primate recipients. In these recipients, C activity slowly returned and C deposition was noted in the Xgs at rejection. To evaluate the effect of sustained C inhibition using sCR1 on HAR, two additional cynomolgus monkeys received porcine cardiac Xgs and a continuous infusion of sCR1. In the first recipient, Xgs survival was 5 days (120+ hr), whereas in the second, Xg survival was 7 days (168+ hr). Serial biopsies of the Xgs were remarkable for an increasing cellular infiltrate composed predominantly of neutrophils and macrophages, and the development of edema, hemorrhage, and myocyte necrosis. These findings suggest that once C-mediated HAR has been inhibited, infiltration of the Xg by these cells may lead to accelerated acute rejection, which is an additional barrier to successful longer term Xg survival.
Pruitt
S K
SK
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Bollinger
R R
RR
Collins
B H
BH
Marsh
H C
HC
Levin
J L
JL
Rudolph
A R
AR
Baldwin
W M
WM
Sanfilippo
F
F
D000818:Animals; D003169:Complement Inactivator Proteins; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000379:methods; D007165:Immunosuppression Therapy / Q000379:methods; D007262:Infusions, Intravenous; D008252:Macaca fascicularis; D015425:Myocardial Reperfusion; D011951:Receptors, Complement / Q000276:immunology*; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000379:methods
D003169:Complement Inactivator Proteins; D011951:Receptors, Complement