Human membrane cofactor protein (MCP, CD 46) protects transgenic pig hearts from hyperacute rejection in primates

Recently, we and others have shown the prolongation of xenograft survival w ith the use of transgenic pigs bearing human CD 59 and DAF complement regul atory proteins (CRP). We now report heart transplantation using a new line of transgenic pigs bearing a different human CRP, membrane cofactor protein (MCP, CD 46). We transplanted three MCP transgenic and three wild-type por cine hearts into baboons suppressed with cyclosporine, methylprednisone, an d rapamycin or cyclophosphamide. In addition, recipients were treated with extracorporeal plasma perfusion to remove alpha -Gal reactivity. The wild-t ype grafts were rapidly rejected at 60 to 80 min. Two functioning MCP heart s were removed after 5 and 46 h for histological examination. One MCP heart showed vigorous function until postoperative day 16. Immunohistochemistry of both wild-type and MCP-transgenic hearts showed strong deposition of IgM . In contrast, there was less MAC deposition in the transgenic graft as com pared to the wild-type control. MCP is another CRP capable of decreasing th e features of hyperacute rejection of cardiac xenografts in baboon recipien ts.