INHIBITION OF C]1 COMPONENT OF COMPLEMENT BY AMINO ACIDS

Abstract

Studies were performed to determine whether epsilon-amino caproic acid (EACA) and related compounds known to inhibit plasminogen activation might also similarly affect immune haemolysis by inhibition of C[image]1 proesterase activation. Long-chain amino acids (six to eight carbon atoms), diamino amino acids and amino alkanes inhibited immune haemolysis, whereas dicarboxylic and fatty acids did not. Inhibition of immune haemolysis by the former group was reversed by the addition of complement reagents R2, R3 and R4 (lacking C[image]2, C[image]3 and C[image]4 components), but not by reagents R0 and R1 (lacking components C[image]0 and C[image]1). These results suggested that the amino group was necessary for inhibition of immune haemolysis by EACA and that EACA inhibited complement activity by reacting with the C[image]0 and C[image]1 components. Since the C[image]1 component of complement was inhibited, the activation of C[image]1 proesterase was studied with the pH stat. The following observations were made (1) The reaction between C[image]1 proesterase and the sensitized red cell produced hydrogen ion and therefore was considered to be enzymatic. (2) This activation reaction was inhibited by EACA and ethylenediamine tetraacetic acid (EDTA). (3) C[image]1 esterase hydrolysed p-tosyl-1-arginine-methyl-ester (TAMe) provided that the system was free of serum or that TAMe was added to the sensitized red blood cells before the complement source (C[image]1). (4) C[image]1 esterase activity, in contrast to C[image]1 proesterase activation, was not inhibited by EACA or EDTA. (5) Addition of increasing amounts of TAMe to the intact haemolytic system resulted in decreased rates of immune haemolysis, together with increased rates of hydrolysis, suggesting that TAMe was competing for the active site of C[image]1 esterase with a natural substrate (C[image]2) essential for haemolysis.