Introduction Human donor organ shortages have led surgeons and scientists to explore the use of animals as alternative
organ sources. Acute thrombovascular rejection (AVR) is the main hurdle in xenotransplantation. Disparities in nucleotide
metabolism in the vessels of different species may contribute significantly to the microvascular component of AVR.
Methods We evaluated the extent of nucleotide metabolism mismatch in selected organs and endothelial cells of different
mammals with particular focus on the changes in activity of ecto-5’-nucleotidase (E5’N) elicited by exposure of porcine hearts
or endothelial cells to human blood (ex vivo) or human plasma (in vitro).
Results E5’N activity in the rat heart was significantly higher than in other species. We noted a significant difference
(p<0.001) in E5’N activity between human and pig endothelial cell lines. Initial pig aortic endothelial E5’N activity decreased
in vitro after a three-hour exposure to human and porcine plasma while remaining constant in controls. Ex vivo perfusion with
fresh human blood for four hours resulted in a significant decrease of E5’N activity in both wild type and transgenic pig hearts
overexpressing human decay accelerating factor (p<0.001).
ConclusionS This study provides evidence that mismatches in basal mammalian metabolic pathways and humoral immunity
interact in a xenogeneic environment. Understanding the role of nucleotide metabolism and signalling in xenotransplantation
may identify new targets for genetic modifications and may lead to the development of new therapies extending graft survival.