Generation of chemotactic factors in guinea pig serum via activation of the classical and alternate complement pathways

Abstract

The characteristics of generation of PMN chemotactic factors by endotoxin and immune complexes have been studied in normal and C4-deficient guinea pig serum. Over a wide dosage range, both activating agents effectively interacted with C4-deficient serum to produce normal levels of chemotactic activity. The appearance of activity was blocked by EDTA or prior heating of the serum, but not by EGTA. The alternate pathway of complement activation, therefore, is capable of mediating efficient generation of chemotactic factors by endotoxin and immune complexes. In studies of the kinetics of generation of chemotactic factors, it was shown that activation of the alternate complement pathway resulted in an initial latent period with subsequent rapid appearance of activity, while classical C142 pathway activation led to very rapid early generation of chemotactic activity. The PMN chemotactic activity generated by either endotoxin or immune complexes resides in two distinct low molecular weight factors (17,000 and 10,000). These factors have been identified as two different C5 cleavage products.