Hyperacute lung rejection in a pig-to-human transplant model: the role of anti-pig antibody and complement.
BACKGROUND
The physiology of hyperacute rejection of pig lung by human blood and the role of antispecies antibody and complement in this phenomenon have not previously been characterized.


METHODS
Human blood was perfused through an ex vivo pig heart-lung preparation. In the treatment groups, blood was either unmodified or modified to deplete alternative pathway complement (heat treatment), anti-pig antibody, or both. Control experiments were performed with unmodified and heat-treated pig blood. Physiologic parameters, organ survival, and immunohistology were the primary outcome measures assessed.


RESULTS
Pig lung was consistently damaged by human blood within 45 min (median 20 min), as evidenced by elevated pulmonary vascular resistance and parenchymal injury. Immunohistologic studies of perfused lungs showed prominent deposition of IgM and classical pathway component, C4, and weaker deposition of alternative pathway component, properdin. Heat treatment did not impede the rise in pulmonary vascular resistance or significantly prolong survival. Depletion of anti-pig antibody prolonged survival (median 90 min) and attenuated the rise in pulmonary vascular resistance. Antibody absorption, combined with heat treatment of plasma, prevented the elevation in pulmonary vascular resistance and yielded median graft survival (210 min) similar to pig blood perfusion (approximately 240 min).


CONCLUSIONS
These results show that elevated pulmonary vascular resistance and pulmonary parenchymal injury are mediated at least in part by antispecies antibody and heat-sensitive pathways. They are consistent with the hypothesis that complement activation contributes significantly to acute lung damage in the pig-to-human species combination.
Pierson
R N
RN
Transplant Unit, Papworth Hospital, Papworth-Evrard, England.
Kasper-Konig
W
W
Tew
D N
DN
Young
V K
VK
Dunning
J J
JJ
Horsley
J
J
Carey
N R
NR
Wallwork
J
J
White
D J
DJ
D000818:Animals; D000906:Antibodies / Q000502:physiology*; D003165:Complement System Proteins / Q000502:physiology*; D006084:Graft Rejection; D006358:Hot Temperature; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D016040:Lung Transplantation / Q000276:immunology*; D010477:Perfusion; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*; D014655:Vascular Resistance
D000906:Antibodies; D007075:Immunoglobulin M; D003165:Complement System Proteins