Heterotoxicity of human serum. IV. Role of the alternative complement pathway and natural antibody in the lethal toxicity of human serum for mice.

The toxic and often lethal reaction caused by intravascular injection of fresh human serum (FHS) was studied in mice. Decomplementation experiments indicated that the alternative complement pathway plays an essential role in the production of 'serum shock'. In vivo activation of human factor B and C3, following the administration of FHS into mice, was detected by immunoelectrophoresis. Absorption experiments suggested that natural antibodies were not required for toxicity, although they may amplify the lethal potential of normal sera by feedback mechanisms of C activation. Injections of FHS caused intravascular hemolysis of mouse erythrocytes and platelet aggregation in mice. The relationship of these observations to the mechanism(s) underlying lethality will be discussed in the following article.