Metabolic behavior of C3 in normal, C4 deficient (C4D) and cortisone treated guinea pigs

C3 was isolated from the pseudoglobulin fraction of guinea pig serum by DEAE and CM cellulose chromatography and Pevikon block electrophoresis. The final product, which was functionally and chemically pure, was radiolabeled with ¹²⁵I by chloramine T and used for turnover studies. In normal guinea pigs, metabolic studies revealed the following: fractional catabolic rate (FCR), 7.9 ± 0.4%/hr (S.E.); synthetic rate, 6.2 ± 0.4 mg/kg/hr; and percent of C3 in the plasma pool, 51 ± 2. The corresponding means were not significantly different in C4 deficient animals, suggesting that activation of the classical complement pathway is not essential for significant C3 turnover in the resting state. Guinea pigs were given 20 (low) or 100 (high) mg cortisone acetate/kg. Serum C3 levels fell 27 ± 6% and 52 ± 5%, respectively, over the course of 2 wk of therapy and stabilized at the lower values. In cortisone treated animals studied during steady state conditions (after 14 days of continuous therapy), the FCR was 9.2 ± 4%/hr and 12.5 ± 7%/hr for the low and high dose groups, respectively. Synthetic rates and percentage of C3 in the intravascular pool were similar in treated and untreated animals. 2 wk after discontinuing therapy, the serum C3 and FCR had returned to normal. Thus, an increased fractional catabolic rate is primarily responsible for the depressed serum levels of C3 observed in cortisone treated animals.