Intact pancreatic islet function despite humoral xenorecognition in the pig-to-monkey combination

Background. The aim of this study was to analyze humoral xenoreactivity of various Old World primate species sera against pig islets and the effects o f these sera on pig islet viability and function after culture. Methods. Freshly isolated or cultured adult pig islets were analyzed by imm unohistology or by cytofluorimetry for Old World primate xenoreactive natur al antibody (XNA) binding and complement deposition. Complement-mediated cy totoxicity was evaluated by Cr-51 release assays. After 4 days of culture i n 50% sera from Old World primates, the morphology and in vitro metabolic f unction of pig islets were also analyzed, Results. Chimpanzee, Macaca mulatta (rhesus), or baboon XNA binding was det ectable only on intra-islet endothelial cells (ECs), Incubation of pig isle ts with sera from all Old World primate species tested showed C3 and C4 dep osition on ECs and on some surrounding endocrine cells. However, membrane a ttack complex (MAC) showed a pattern of positivity similar to XNA binding, i,e., restricted to ECs only. No deposition of factor B was detected, Altho ugh complement cascade was activated, no cytotoxicity was observed after in cubation of islets with chimpanzee serum, whereas between 10% and 35% Cr-51 specific release was obtained with rhesus, baboon, or Macaca fascicularis sera, Despite this cytotoxic effect, purified pig islets showed a normal mo rphology and a well-preserved insulin release in response to an acute gluco se stimulus, after prolonged culture with 50% serum obtained from all prima te species considered. Conclusions. Despite the fact that pig beta-cell function was not affected by the serum of any of the primate species tested, some of them yielded sig nificant lysis of islet cells, presumably as a result of a cytotoxic effect on intra-islet ECs, These data show that Old World primate sera from diffe rent species do not have equivalent effect on pig islets; these differences should be taken into account in preclinical trials of pig islet xenotransp lantation.