The neutrophil: the unnoticed threat in xenotransplantation?
BACKGROUND
Xenotransplantation offers one way to circumvent the widening gap between the demand for and supply of human organs for transplantation, and the pig is widely regarded as the donor animal most likely to prove appropriate. Most attention has focused on the adaptive immune response to xenogeneic tissue. However, there is optimism that it may soon be possible to overcome that hurdle. In this paper, we consider the possibility of the direct recognition of xenogeneic tissue by neutrophils.


METHODS
We studied in vitro the interaction of human neutrophils with cultured porcine endothelial cells in assays of adhesion (both static and flow), activation on the basis of chemiluminescence, and diapedesis and chemotaxis using split-well chambers.


RESULTS
Human neutrophils showed increased adhesiveness to porcine endothelium in both static and flow adhesion systems. While this did not activate the neutrophils at rest, in the presence of suboptimal concentrations of a parallel stimulus, phorbol myristate acetate, the interaction of human neutrophils with porcine endothelium caused a much greater respiratory burst than their interaction with controls. In addition, they showed greater diapedesis through porcine endothelium. Of greatest interest is the observation that porcine endothelium secretes a molecule that is chemotactic for human neutrophils.


CONCLUSIONS
On the basis of these observations, we should consider the potential for neutrophil-mediated low-grade damage to xenografts emerging as a significant problem when others have been circumvented.
Cardozo
Lorraine A M
LA
Department of Immunology, Hammersmith Campus, Imperial College London, London, United Kingdom.
Rouw
Dennis B
DB
Ambrose
Lyn R
LR
Midulla
Marta
M
Florey
Oliver
O
Haskard
Dorian O
DO
Warrens
Anthony N
AN
D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D008163:Luminescent Measurements; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D016897:Respiratory Burst; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*