Role of the classical and alternative complement pathways in chemotaxis and opsonization: studies of human serum deficient in C4

The roles of the classical and alternative C pathways in the formation of chemotactic factors and opsonins in human serum were evaluated by comparative studies on normal serum and serum from a patient with a nonfunctional classical pathway resulting from an inherited absence of C4. Neutrophil chemotactic activity was determined in serum activated by zymosan, bacterial endotoxin, intact bacteria, and cobra venom factor, by using a ⁵¹Cr radioassay in Boyden chambers. Opsonization of zymosan by serum was determined by the iodination reaction with human neutrophils as the test cells. Chemotactic activity and opsonization were both markedly impaired in C4-deficient serum; these defects were most apparent when the serum concentration was low or the period of exposure to the activating agent was short. Normal chemotactic and opsonic activity was observed when either the serum concentration or the incubation time was increased with zymosan as the activating agent. In contrast, correction of the chemotactic defect was not achieved under similar conditions when endotoxin was the activating agent. The addition of purified C4 resulted in improvement or normalization of chemotactic and opsonic function. Similar defects were demonstrated in sera from an unrelated patient with inherited C4 deficiency and from a patient with absent C4 and C2. These observations point out the necessity for an intact classsical pathway in order to achieve optimal formation of biologic mediators from the C system.