Activation of naive xenogeneic but not allogeneic endothelial cells by human naive neutrophils: a potential occult barrier to xenotransplantation.

Here we demonstrate that human neutrophils, the predominant circulating leukocytes in intimate contact with endothelial cells lining the vasculature, directly recognize xenogeneic endothelium independently of xenoreactive natural antibody and complement. A rapid and calcium-dependent activation of native (unstimulated) xenogenic endothelial cells by human neutrophils leads to 1) translocation of P-selectin from the Wiebel-Palade bodies to the surface of xenogeneic endothelial cells, 2) increased synthesis and expression of vascular cell adhesion molecule-1 on the xenogeneic endothelial cells, and 3) enhanced killing of the xenogeneic endothelium by natural killer cells. Our data directly implicate naive neutrophils as major early participants in xenograft recognition and endothelial activation independent of xenoreactive natural antibodies and complement.