Depletion of pulmonary intravascular macrophages prevents hyperacute pulmonary xenograft dysfunction.
BACKGROUND
Recent years have brought dramatic progress in the field of xenotransplantation, with the development of transgenic swine and various other means of overcoming the rejection mediated by xenoreactive antibodies. Although progress has been rapid with kidney and heart xenografts, progress with pulmonary xenografts has lagged behind. Recent findings have suggested that donor pulmonary intravascular macrophages may play a critical role in the hyperacute dysfunction of pulmonary xenografts.


METHODS
The function of pulmonary xenografts from pigs depleted of pulmonary intravascular macrophages was compared with the function of xenografts from normal pigs.


RESULTS
Pulmonary xenografts from pigs from which pulmonary intravascular macrophages were depleted survived (23.5+/-0.9 hours) about five times longer than normal (macrophage sufficient) xenografts (4.4+/-1.41 hours) (P< 0.0001). At 21 hours post-reperfusion, the left pulmonary arterial flow was 225.0+/-34 ml/min in lungs depleted of pulmonary intravascular macrophages, whereas all normal xenografts had failed.


CONCLUSIONS
These findings indicate that donor macrophages play a critical role in pulmonary xenograft dysfunction. This finding has broad implications for xenotransplantation, suggesting that porcine macrophages might pose a barrier to the engraftment and function of a variety of porcine organ xenografts.
Cantu
Edward
E
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Gaca
Jeffrey G
JG
Palestrant
Daniel
D
Baig
Kamran
K
Lukes
Daniel J
DJ
Gibson
Sarah E
SE
Gonzalez-Stawinski
Gonzalo V
GV
Olausson
Michael
M
Parker
William
W
Davis
R Duane
RD
D000818:Animals; D001794:Blood Pressure; D015936:Complement C5a / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D006085:Graft Survival; D006339:Heart Rate; D008168:Lung / Q000098:blood supply / Q000473:pathology; D016040:Lung Transplantation / Q000009:adverse effects*; D008264:Macrophages / Q000502:physiology*; D010215:Papio; D011652:Pulmonary Circulation; D013552:Swine; D014183:Transplantation, Heterologous / Q000009:adverse effects*; D014655:Vascular Resistance
D015936:Complement C5a