Blocking porcine sialoadhesin improves extracorporeal porcine liver xenoperfusion with human blood.

Background Patients in fulminant hepatic failure currently do not have a temporary means of support while awaiting liver transplantation. A potential therapeutic approach for such patients is the use of extracorporeal perfusion with porcine livers as a form of 'liver dialysis'. During a 72-h extracorporeal perfusion of porcine livers with human blood, porcine Kupffer cells bind to and phagocytose human red blood cells (h RBC) causing the hematocrit to decrease to 2.5% of the original value. Our laboratory has identified porcine sialoadhesin expressed on Kupffer cells as the lectin responsible for binding N-acetylneuraminic acid on the surface of the h RBC. We evaluated whether blocking porcine sialoadhesin prevents the recognition and subsequent destruction of h RBCs seen during extracorporeal porcine liver xenoperfusion. Methods Ex vivo studies were performed using wild type pig livers perfused with isolated h RBCs for 72-h in the presence of an anti-porcine sialoadhesin antibody or isotype control. Results The addition of an anti-porcine sialoadhesin antibody to an extracorporeal porcine liver xenoperfusion model reduces the loss of h RBC over a 72-h period. Sustained liver function was demonstrated throughout the perfusion. Conclusions This study illustrates the role of sialoadhesin in mediating the destruction of h RBCs in an extracorporeal porcine liver xenoperfusion model. [ABSTRACT FROM AUTHOR]