In vitro accommodation of porcine endothelial cells by low dose human anti-pig antibody: Reduced binding of human lymphocytes by accommodated cells associated with increased nitric oxide production

Transplanted xenografts, protected from rejection by depletion of xenoreactive natural antibodies (XNA) and complement, can sometimes survive when complement levels and titres of anti-graft antibodies return to baseline; this phenomenon is called accommodation. We have previously reported that low concentrations of human IgG induce a change in the phenotype of immortalised porcine endothelial cells (IPEC) consistent with the development of accommodation, The cells acquired a resistance to lysis by human complement and showed a reduced expression of VCAM. In this study, we extend these findings by showing that VCAM expression falls on several IPEC clones and on primary porcine endothelial cells. Moreover, we show that these accommodated cells bind fewer human lymphocytes compared to controls, implying that leukocyte traffic through accommodated endothelium may be altered compared to that through normal endothelium. Finally we show that during the induction of accommodation, porcine endothelial cells produce greater amounts of nitric oxide than controls, due to the expression of inducible nitric oxide synthase (iNOS). We speculate that nitric oxide may be an important mediator in accommodation.