Xenoreactive antibodies (Ab) are important for the development of acute vascular rejection (AVR) of xenografts characterized by monocytes, natural killer (NK) cells and neutrophils infiltrating the graft. The mechanisms by which anti-galactose § 1,3galactose ( § -Gal) IgG influence NK cell migration across porcine aortic endothelium (PAEC) were investigated. NK cell migration across PAEC increased in the presence of anti- § -Gal IgG. Anti- § -Gal IgG exposure activated PAEC as shown by an increased expression of CD62E and CD106. NK cells adhered, spread and showed motile forms on plastic surfaces coated with human IgG, IgG Fc and on mAb against CD16, but not on mouse IgG or BSA, suggesting that CD16 cross-linking can mediate increased adhesiveness. Increased NK cell motility was observed on Boyden filters coated with human IgG, IgG Fc, and mAb against CD16 and the § 4, § 5, § L, g 1 and g 2 integrin chains. No motile response was seen on mouse IgG or CD7, CD56 and § 6 integrin mAb. NK cell migration on human IgG and anti-CD16 Ab was blocked by anti-CD16 or anti-g 2, but not anti-g 1 Ab, implying that the motile response triggered by CD16 cross-linking is mediated via g 2 integrins. Preformed or induced anti- § -Gal IgG may therefore contribute to AVR by stimulating innate immune cell infiltration of the graft.