THE KINETICS AND DISTRIBUTION OF C9 AND SC5B-9 IN-VIVO - EFFECTS OF COMPLEMENT ACTIVATION

Many diseases associated with complement activation are characterized by tissue deposition of components of the terminal complement complex (TCC). The ninth component of complement (C9) plays an important role in the cytolytic effects, and may contribute to the non-lethal cell-re gulating functions of the TCC [1]. In this study we examined the behav iour of radiolabelled human C9 and its soluble complexed form SC5b-9 i n vivo in order to determine the effects of complement activation on i ts turnover, distribution and molecular size. In normal rabbits the me tabolic parameters of I-125-C9 (median and range) were: plasma half-li fe (t(1/2)) 25.9 (20.6-29.5) h, fractional catabolic sate (FCR) 5.7 (5 .3-7.0)%/h, and extravascular/intravascular ratio (EV/IV) 0.7 (0.6-1.1 ). The distribution of radiolabelled C9 amongst body tissues was simil ar to that observed for rabbit serum albumin (RSA). Activation of the complement cascade with i.v. injection of cobra venom factor (CVF) res ulted in rapid disappearance of C9 from the plasma and accumulation of protein-bound radiolabel in the spleen (exceeding the plasma concentr ation) and the liver. RSA metabolism and distribution were unaffected by CVF. Fine performance liquid chromatography (FPLC) gel filtration o f plasma samples suggested that monomeric C9 was the only major radiol abelled protein present during normal turnovers, whereas CVF administr ation was accompanied by the prompt appearance of a high mol. wt speci es consistent in size with SC5b-9. When injected directly, I-125-SC5b- 9 disappeared rapidly from the plasma, falling by 50% in 0.7 (0.6-0.8) h, and less than 15% remaining after 4 h with accumulation of protein -bound label in the spleen and liver. These results demonstrate the co mplexity of C9 metabolism during complement activation.