Mechanism of complement activation by radiographic contrast media

Activation of the complement system by radiographic contrast media (RCM) was demonstrated by in vitro haemolytic and immunological assays. Such activation was found to be a function of the RCM molar concentration. Iodipamide was the most active of five RCM tested. When RCM was incubated with normal human serum (NHS) in the presence of ethylene glycol-tetra-acetic acid and magnesium ions, conditions which block activation of the classical pathway but permit activation of the alternative pathway, haemolytically active C3, properdin and factor B were found to be decreased but haemolytically active C4 was normal. Using counterimmunoelectrophoresis, the activation of complement was further demonstrated by detection of C3 and factor B-split products. Finally, when radiolabelled complement proteins were reacted with RCM in vitro and studied by density-gradient ultracentrifugation, it was demonstrated that a large complex was formed with a sedimentation of 22S, similar in characteristics to the C5b-C9 complex. It was postulated that the mechanisms of in vitro consumption of complement by RCM was mainly through the alternative pathway.