Different mechanisms mediate the rejection of porcine neurons and endothelial cells transplanted into the rat brain

In order to investigate the early cellular responses mediating xenograft re jection in the brain, porcine aortic endothelial cells (PAEC) or porcine fe tal mesencephalic neurons (PNEU) were transplanted into the striatum of LEW .1A rats. PAEC were detected with a specific anti-beta1 integrin antibody, and PNEU with an anti-porcine neurofilament antibody, or an antibody recogn izing the NeuN antigen. PAEC grafts were massively infiltrated within 24 h by OX42-positive cells, which may correspond to polymorphonuclear (PMN) cel ls or macrophages. At that moment, the graft contained numerous cells expre ssing the inducible isoform of NO-synthase (iNOS). Infiltration by EDI-posi tive macrophages was effective after three days. The beta1-integrin labelin g decreased from that time-point to day 7 post-implantation, and vanished a fter 11 days. Although some OX8-positive cells were present around the graf t as soon as 3 days after transplantation, cells expressing the T-cell rece ptor (TCR)-beta chain infiltrated the graft after 7 days and their number r emained low. A strong, diffuse OX8-and ED1-positive immunoreactive material remained in the scar up to the third week. In striking contrast, PNEU graf ts remained poorly infiltrated by OX42- or EDI-positive cells during the fi rst two weeks. A massive infiltration by macrophages and TCR beta -positive lymphocytes occurred after 3 weeks. Natural killer (NK) cells were more sc arce. The inflammation territory enlarged, and blood vessels were overloade d with macrophages or lymphocytes. Nevertheless, the graft contained NeuN-p ositive nuclei and neurites harbouring the porcine neurofilament protein. H ence, rejection was not completed at this time-paint. These results suggest that the rapid rejection of PAEC is mainly driven by macrophages and possi bly PMN cells, unlike PNEU, whose rejection is delayed and also involves ly mphocytes. Differences in immunogenicity of grafted cells and/or patterns o f production of pro-inflammatory cytokines may account for these contrasted rejection kinetics.