Identification of antigens on porcine pulmonary microvascular endothelial cells recognized by human xenoreactive natural antibodies

Transplantation of organs between species is prevented in part by humoral immune responses triggered by xenoreactive natural antibodies. Although the immune barrier to xenotransplantation of the lung is thought to be qualitatively and quantitatively different than the immune barrier to xenotransplantation of the kidney or heart, the antibody-antigen reactions responsible for rejection of pulmonary xenografts have not been characterized. To begin to address this issue for porcine lungs transplanted into humans, we analyzed the porcine pulmonary endothelial antigens recognized by human xenoreactive natural antibodies. Human and baboon natural antibodies recognized glycoprotein and glycolipid antigens isolated from the membranes of porcine pulmonary microvascular endothelial cells. The antigens included the integrin chains alpha(1), alpha(2), alpha(3), alpha(5), alpha(nu), beta(1), beta(3), the von Willebrand Factor, and fibronectin. These glycoproteins seemed to be recognized by the same antibodies that bind to porcine kidney or cardiac xenografts. Natural antibodies also recognized at least four glycolipids containing from one to five sugar residues, although at a lower level per unit number of cells than glycoprotein antigens. The epitope recognized by natural antibodies was predominantly Gal alpha 1-3Gal, a structure expressed by lower mammals but not by humans and baboons. The antigens recognized by human antibodies in the porcine lung may provide insight into the pathogenesis of the rejection reaction. Moreover, the similarity of porcine lung antigens to porcine kidney and heart antigens suggests that differences in the rejection reactions between these organs reflects the distinct responses of the organs to humoral immunity.