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 i mmune responses triggered by xenoreactive natural antibodies. Although the immune barrier to xenotransplantation of the lung is thought to be qualitat ively and quantitatively different than the immune barrier to xenotransplan tation of the kidney or heart, the antibody-antigen reactions responsible f or rejection of pulmonary xenografts have not been characterized. To begin to address this issue for porcine lungs transplanted into humans, we analyz ed the porcine pulmonary endothelial antigens recognized by human xenoreact ive natural antibodies. Human and baboon natural antibodies recognized glyc oprotein and glycolipid antigens isolated from the membranes of porcine pul monary 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 c ontaining from one to five sugar residues, although at a lower level per un it number of cells than glycoprotein antigens. The epitope recognized by na tural 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 pathogene sis of the rejection reaction. Moreover, the similarity of porcine lung ant igens to porcine kidney and heart antigens suggests that differences in the rejection reactions between these organs reflects the distinct responses o f the organs to humoral immunity.