Mechanisms of Leukocyte Regulation by Complement-Derived Factors

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Abstract
As early as the mid-1960s it was recognized that factors derived from the blood complement system could stimulate leukocytes and promote directed leukocyte migration (Ward et al., 1965, 1967; Shin et al., 1968; Snyderman et al., 1968). Shortly thereafter assignments were made that identified anaphylatoxins as the humoral chemotactic factors in question (Jensen et al., 1969; Hill and Ward, 1969; Ward 1967, 1969; Cochrane and Müller-Eberhard, 1968; Fernandez et al., 1978). Anaphylatoxins are low-molecular-weight fragments released from serum components C3, C4, and C5 when the complement cascade is activated; these fragments have been designated C3a, C4a, and C5a, respectively. Several recent reviews describe the properties of the anaphylatoxins in great detail (Hugli and Müller-Eberhard, 1978; Hugli, 1978, 1981, 1982). Before the anaphylatoxins were identified as chemotaxins, they were noted primarily for their spasmogenic and permeability-enhancing activities, mediated largely via vasoamines released from the mast cell (Johnson et al., 1975). However, it was the recognition of neutrophil-anaphylatoxin interactions, using chemotaxis as an indicator of cellular activation, that prompted discovery of numerous other leukocyte responses mediated by these anaphylatoxins. The current status of our knowledge concerning the multiple effects of the anaphylatoxins on leukocyte function is the subject of this chapter.