CROSS-SPECIES INTERACTION OF PORCINE AND HUMAN INTEGRINS WITH THEIR RESPECTIVE LIGANDS - IMPLICATIONS FOR XENOGENEIC TOLERANCE INDUCTION

Background, Organ transplantation is limited by the number of availabl e donors. One possible solution would be the use of pigs as organ dono rs. However, current immunosuppressive protocols cannot prevent reject ion of these organs. If donor-specific tolerance toward porcine antige ns could be induced in recipients, subsequent implantation of porcine organs would be possible without further immunosuppression. Induction of tolerance can be achieved with a bone marrow transplant if donor an tigen presenting cells successfully differentiate in the recipient thy mus to induce deletion of donor-reactive host cells. Migration of porc ine progenitor cells to the host marrow and thymus and differentiation into tolerance-inducing antigen-presenting cells is likely to require successful interaction of porcine adhesion molecules with human ligan ds. In this study, we investigated whether very late antigen (VLA)-4 a nd VLA-6 integrins, which play important roles in homing and different iation of hematopoietic progenitor cells, function across the pig-to-h uman species barrier. Methods. Static cell-to-cell and cell-to-extrace llular matrix protein adhesion assays were used to examine the cross-s pecies interaction of porcine adhesion molecules with human ligands. R esults. Our studies show that porcine cells adhere to various human en dothelial cell monolayers and extracellular matrix proteins and demons trate that porcine VLA-4 and VLA-6 appear to be fully cross-reactive t o the human ligands vascular cell adhesion molecule-1 and laminin, res pectively. Conclusions. It is likely that porcine hematopoietic progen itor cells will be able to successfully employ pVLA-4- and pVLA-6-huma n ligand interactions in a pig-to-human bone marrow transplantation mo del in order to induce donor-specific tolerance.