Human complement regulatory proteins protect swine lungs from xenogeneic injury.
BACKGROUND
Pulmonary xenotransplantation is not possible because of hyperacute lung injury, the pathogenesis of which is unknown. This study evaluates complement-dependent pathways of pulmonary injury during heterologous perfusion of swine lungs.


METHODS
Lungs from unmodified swine and swine expressing human decay-accelerating factor and human CD59 (hDAF/hCD59 swine) were perfused with either human plasma or baboon blood. Pulmonary vascular resistance and static pulmonary compliance were measured serially, and swine lung tissue were examined by light microscopy. Complement activation was assessed by serial measurements of baboon plasma C3a-desArg concentrations.


RESULTS
Perfusion of unmodified swine lungs with human plasma and baboon blood resulted in hyperacute lung injury within minutes of perfusion. However, function was preserved in swine lungs expressing human decay-accelerating factor and human CD59. In both study groups, xenogeneic perfusion with baboon blood resulted in at least a sevenfold increase in plasma C3a-desArg levels suggesting transient activation of complement.


CONCLUSIONS
Lungs from swine expressing human decay-accelerating factor and human CD59 were resistant to injury during perfusion with human plasma and baboon blood, indicating that complement mediated some of the features of xenogeneic acute lung injury.
Yeatman
M
M
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Daggett
C W
CW
Lau
C L
CL
Byrne
G W
GW
Logan
J S
JS
Platt
J L
JL
Davis
R D
RD
D000818:Animals; D001769:Blood; D018958:CD55 Antigens / Q000378:metabolism / Q000502:physiology*; D018957:CD59 Antigens / Q000378:metabolism / Q000502:physiology*; D003165:Complement System Proteins / Q000502:physiology*; D005112:Extracorporeal Circulation; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016040:Lung Transplantation; D010215:Papio; D010477:Perfusion; D011652:Pulmonary Circulation; D013552:Swine; D014183:Transplantation, Heterologous
D018958:CD55 Antigens; D018957:CD59 Antigens; D003165:Complement System Proteins