Analysis of chemotactic factor generation in C1q-deficient sera

The roles of the classical and alternative complement pathways in the formation of chemotactic factors in normal human serum and in sera from patients with an inherited selective deficiency of C1q were studied. Monocytic chemotaxis was evaluated in serum activated by zymosan, endotoxin, cobra venom factor, aggregated human IgG and immune complexes. Chemotactic activity was only impaired when the C1q-deficient serum concentration was low or the period of exposure to zymosan, endotoxin or immune complexes was short. No effect was demonstrated when cobra venom factor and aggregated human IgG were used as activating agents even at limited serum concentrations. Chemotactic activity was also impaired when deficient sera were chelated with EGTA and activated with immune complexes during 7 and 60 min. The addition of normal human serum or purified human C1q to the assay resulted in improvement or normalization of the chemotactic function. The observation that the formation of chemotactic factors via the alternative pathway requires a higher serum concentration and/or longer activation time, points out the necessity for an intact classical pathway in order to achieve optimal activation of the alternative pathway.