Immunoglobulin prevents complement-mediated hyperacute rejection in swine-to-primate xenotransplantation.
Immunoglobulins regulate the complement system by activating complement on foreign surfaces and diverting reactive complement proteins away from autologous cell surfaces. Based on this model, we explored the ability of Ig to balance complement activation versus control in a pig-to-primate cardiac xenotransplantation model in which the binding of xenoreactive antibodies of the recipient to graft blood vessels and the activation of complement cause hyperacute rejection. Human IgG added to human serum caused a dose-dependent decrease in deposition of iC3b, cytotoxicity, and heparan sulfate release when the serum was incubated with porcine endothelial cells. This decrease was not caused by alteration in antibody binding or consumption of complement but presumably reflected decreased formation of C3 convertase on the endothelial cells. Infusion of purified human IgG into nonhuman primates prevented hyperacute rejection of porcine hearts transplanted into the primates. As expected, the transplants contained deposits of recipient Ig and C1q but not other complement components. The inhibition of complement on endothelial cell surfaces and in the xenotransplantation model supports the idea that IgG regulates the classical complement pathway and supports therapeutic use of that agent in humoral-mediated disease.
Magee
J C
JC
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Collins
B H
BH
Harland
R C
RC
Lindman
B J
BJ
Bollinger
R R
RR
Frank
M M
MM
Platt
J L
JL
D000818:Animals; D003176:Complement C3 / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D011323:Primates; D013552:Swine; D014183:Transplantation, Heterologous
D003176:Complement C3; D007074:Immunoglobulin G; D007075:Immunoglobulin M