508 Porcine xenografts transplanted into primate recipients undergo a T cell-independent cellular rejection process which is mediated largely by monocytes/macrophages and natural killer (NK) cells. Following culture with porcine aortic endothelial cells (PAEC), human NK cells produced high levels of IFN gamma, which augmented human monocyte adhesion to PAEC by over 2.5-fold. Interactions of resting human monocytes with PAEC involved binding through CD62L, whereas PAEC binding of IFN gamma activated monocytes additionally involved CD69 receptors. The tyrosine kinase inhibitor genistein inhibited both IFN gamma-mediated induction of CD69 expression and augmentation of monocyte adhesion, but had minimal effect on adhesion of resting monocytes. Treatment of PAEC with neuraminidase and beta galactosidase sequentially, or with Mabs against sialylated Lewis X antigen (sLeX), inhibited monocyte adhesion. Moreover, adhesion of both resting and IFN gamma-activated monocytes was inhibited more effectively by soluble oligosaccharides containing terminal alpha 2,3-linked sialylated residues than by those containing terminal alpha 2,6-linked sialylated residues. Together, these results suggest that porcine endothelium expresses ligands for human C-type lectins which contain capping structures analogous to those of human GlyCAM. Since in vivo studies of rejected porcine xenografts revealed CD62L and CD69 expression on infiltrating macrophages and sLeX expression on PAEC, these lectin-carbohydrate adhesive interactions are directly relevant to the process of delayed porcine xenograft rejection in primates. This process appears to be T cell-independent, driven by NK cells, and augmented by a tyrosine kinase-dependent activation pathway.