The transgenic expression of human CD39 on murine islets inhibits clotting of human blood.

Platelet activation is believed to play an important role in the triggering of thrombosis of human blood by pig islets. We used a transgenic mouse model to investigate whether overexpression of CD39 (ecto nucleoside triphosphate diphosphohydrolase 1 [ENTPD1], EC 3.6.

Overexpression of glutathione peroxidase with two isoforms of superoxide dismutase protects mouse islets from oxidative injury and improves islet graft function.

Primary nonfunction of transplanted islets results in part from their sensitivity to reactive oxygen species (ROS) generated during the isolation and transplantation process. Our aim was to examine whether coexpression of antioxidant enzymes to detoxify multiple ROS increased the resistance of mouse islets to oxidative stress and improved the initial function of islet grafts. Islets from transgenic mice expressing combinations of human copper/zinc superoxide dismutase (SOD), extracellular SOD, and cellular glutathione peroxidase (Gpx-1) were subjected to oxidative stress in vitro.

Thromboregulatory manifestations in human CD39 transgenic mice and the implications for thrombotic disease and transplantation.

Extracellular nucleotides play an important role in thrombosis and inflammation, triggering a range of effects such as platelet activation and recruitment, endothelial cell activation, and vasoconstriction. CD39, the major vascular nucleoside triphosphate diphosphohydrolase (NTPDase), converts ATP and ADP to AMP, which is further degraded to the antithrombotic and anti-inflammatory mediator adenosine. Deletion of CD39 renders mice exquisitely sensitive to vascular injury, and CD39-null cardiac xenografts show reduced survival.

Enhanced expression of glutathione peroxidase protects islet beta cells from hypoxia-reoxygenation.

The survival of pancreatic islet beta-cell xenografts and allografts may be affected by damaging reactive oxygen and nitrogen species generated during hypoxia-reoxygenation. Peroxynitrite, which is formed from superoxide and nitric oxide, appears to be an important mediator of beta-cell destruction. The intracellular antioxidant enzymes glutathione peroxidase-1 (Gpx-1) and copper-zinc superoxide dismutase (CuZn SOD) detoxify peroxynitrite and superoxide, respectively.