Extrahepatic synthesis of C6 in the rat is sufficient for complement - Mediated hyperacute rejection of a guinea pig cardiac xenograft

The liver is the major source of complement (C) components, but extrahepatic sources of C, such as macrophages and endothelial cells, have been hypothesized to contribute to inflammation. Our experiments demonstrate that extrahepatically produced Cβ can contribute to hyperacute rejection. PVG (RT1C) rats with normal C activity (PVG (C+)) reject guinea pig cardiac xenografts in 0.5±0.2 hr, but fully C6-defîcient PVG (RT1C) rats (PVG (C-)) reject guinea pig cardiac xenografts in 45±9 hr. PVG (C+) rats, which received liver transplants from PVG (C-) rats and retained all extrahepatic sources of Cβ, rejected guinea pig cardiac xenografts in 0.6±0.03 hr (n=3). PVG (C—) rats, which received bone marrow transplants from PVG (C+) rats, had Cβ levels restored to 10% of that of the donor and rejected guinea pig cardiac xenografts in 9±3.2 hr (n=5). Thus, extrahepatic sources of Cβ can contribute to xenograft rejection.