Functional activity of anti-C6 antibodies elicited in C6-deficient rats reconstituted by liver allografts: Ability to inhibit hyperacute rejection of discordant cardiac xenografts

A critical role of the complement membrane attack complex (C5b-9) in mediating hyperacute rejection has been demonstrated previously in fully C6- deficient PVG (C-) (RT1(c)) rats that reject guinea pig cardiac xenografts at a delayed tempo (45±9 hr; n=16) compared with C6-sufficient PVG (C⁺) (RT1(c)) hosts (0.5±2 hr; n=6). We have investigated whether selective depletion of C6 from Lewis rats by antibody therapy prevents hyperacute rejection. A polyclonal rat-antirat C6 antibody was induced in PVG (C^-) recipients by orthotopic liver transplants from congenic PVG (C⁺) donors. These liver grafts produced high levels of C6 that reconstituted the complement function of PVG (C^-) hosts by 7 days, but the recipients responded within 28 days with the synthesis of an IgG1 antibody to rat C6. The antiserum inhibited hemolytic complement activity of Lewis (RT1₁) rats in vivo and in vitro. The effect of C6 depletion on Xg survival was investigated by injecting Lewis rats with 2 ml of rat-antirat C6 antiserum before and 1 ml after reperfusion of the guinea pig cardiac xenograft. Lewis rats rejected guinea pig cardiac xenografts after treatment with this rat- antirat C6 antiserum in 38±11 hr (n=3). Treatment with normal control sera from PVG (C) rats did not prolong guinea pig cardiac xenograft survival in the Lewis rats (1±0.7 hr; n=3) (P