HEPATIC AND EXTRAHEPATIC BIOSYNTHESIS OF COMPLEMENT FACTOR C6 IN THE RAT

The relative contributions of liver and bone marrow (BM) constituents to systemic C6 production were compared in a rat model. Liver grafts w ere transplanted from CG-sufficient PVG (RT1(C)) rats (PVG (C+)) to pr ofoundly C6-deficient PVC rats (PVG (C-)). C6 levels were restored to 32% within 24 h and reached more than 80% of that of the PVG (C+) dono r within 7 days post-grafting, which indicates that the liver is a pri mary source of systemic C6 production. When livers were transplanted f rom PVG (C-) to PVC (C+) rats (n = 3), levels of C6 dropped to 42% of pretransplant levels within 24 h and remained between 30 and 40% for m ore than 100 days after grafting. To determine the source of extrahepa tic C6 production, BM was transplanted from PVG (C+) to PVG (C-) rats after total body irradiation. Levels of C6 increased from undetectable levels to 5% of C6 levels of the donor PVG (C+) rat within 60 days. R eplenishing PVG (C-) recipients with BM after treatment of recipients with busulfan, which preferentially allows reconstitution with donor m yelomonocyte stem cells, resulted in restoration of C activity. Treatm ent with cyclophosphamide before BM transplantation, which preferentia lly allows reconstitution of lymphoid stem cells, did not restore hemo lytic C activity in PVC (C-) rats. These results were confirmed direct ly by the successful restoration of C activity with BM depleted of lym phocytes by counterflow centrifugal elutriation from PVG (C+) rats. Th ese in vivo experiments demonstrate that the liver is a primary, but n ot the sole, source of C6 in the rat and that extrahepatic sources, su ch as myelomonocytes, and not lymphoid cells in the BM produce a signi ficant amount of systemic C6 in the rat.