The kinetics and distribution of C9 and SC5b-9 in vivo: effects of complement activation

Abstract

SUMMARYMany diseases associated wilh 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 cellregulating functions ofthe TCC [1]. In this study we examined the behaviour of radiolabelled human C9 and its soluble complexed form SC5b-9 in vivo in order to determine the effects of complement activation on its turnover, distribution and molecular size. In normal rabbits the metabolic parameters of'^^I-C9 {median and range) were: plasma half-life (/[/2)25'9 (20-6 29-5) h, fractional catabolic rate (FCR) 5-7 (5'3-7'0)%/h. and extravascular/lntravascular ratio (EV/IV) 0'7 (0-6-11). The distribution of radiolabelled C9 amongst body tissues was similar to that observed for rabbit serum albumin (RSA). Activation ofthe complement cascade with i.v. injection of cobra venom factor (CVF) resulted in rapid disappearance of C9 from the plasma and accumulation of protein-bound radiolabel in the spleen (exceeding !he plasma concentration) and the liver. RSA metabolism and distribution were unaffected by CVF. Fine performance liquid chromatography (FPLC) gel filtration of plasma samples suggested that monomeric C9 was the only major radiolabelled protein present during normal turnovers, whereas CVF administration was accompanied by the prompt appearance of a high mol. wt species consistent in size with SC5b-9. When injected directly, '"^I-SC5b-9 disappeared rapidly from the plasma, falling by 50% in 0 7 (0-6-()-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 complexity of C9 metabolism during complement activation.Keywords C9 terminal complement complex metabolic turnover tissue distribution SC5b-9

Complement and Cardiovascular Disease - The Missing Link in Haemodialysis Patients?

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