In vivo metabolism of complement

Abstract

The in vivo metabolism of purified third component of complement labeled with ¹²⁵-iodine (C′3-¹²⁵I) was studied in normal subjects and in patients with acquired hemolytic anemias. 27 such studies were performed; in addition, three studies were performed using C′3i, the biologically inactive reaction product of C′3. In normal subjects the mean fractional catabolic rate of C′3 was 2.12%/hr and the normal range (defined throughout as the mean ± 2 SD) was from 1.56 to 2.68. The mean percentage of C′3 that was intravascular was 66.6% and the normal range was from 51 to 83. The C′3 synthesis rate averaged 1.16 mg/kg per hr with a normal range of from 0.90 to 1.42. The mean serum concentration of C′3 was 1.43 mg/ml with a normal range of from 1.00 to 1.87. The fractional catabolic rate and synthesis rate of C′3 were at the upper limit of normal or were increased above normal in patients who had warm antibody autoimmune hemolytic anemia with complement on their erythrocytes and in patients with paroxysmal nocturnal hemoglobinuria studied during periods of active hemolysis. An increased C′3 synthesis rate was also found in one patient who was hematologically normal but had an active peptic ulcer and elevated serum concentration of C′3. A normal fractional catabolic rate and C′3 synthesis rate were found in patients with autoimmune hemolytic anemia associated with α-methyldopa administration, atypical cold antibody autoimmune hemolytic anemia, and in paroxysmal nocturnal hemoglobinuria during an asymptomatic interval. The three studies with C′3i-¹²⁵I revealed a very rapid removal of the labeled protein from the plasma with less than 10% remaining after 2 hr and with a corresponding increase in urinary excretion rate of the label. The fractional catabolic rate of C′3i averaged 37%/hr. The findings are consistent with the previously elucidated in vitro reaction mechanism of C′3 and strengthen the concept that serum complement participates in immune reactions in vivo.