Contributions of the Classical and Alternate Complement Pathways to the Biological Effects of Endotoxin

Abstract

The interactions of endotoxin with sera from normal guinea pigs and sera from C4-deficient (C4D) guinea pigs that had a complete block in function of the classical complement sequence were examined. Endotoxin fixed the late components of complement (C3–C9) in both normal and C4D sera, demonstrating the existence of an alternate pathway that bypasses the early components of complement. Activation of the alternate pathway generates normal quantities of chemotactic factors, and the kinetics of chemotactic-factor generation is normal. The alternate pathway can opsonize bacteria and mediate the bactericidal reaction, although a difference in kinetics was observed. However, injection of endotoxin into normal and C4D animals revealed that activation of the classical pathway was an absolute requirement for thrombocytopenia and for induction of the hypercoagulable state.