Anaphylatoxins

In addition to the basic functions, opsonization and cytolysis, associated with the complement system there are some physiological activities elicited by complement peptides which contribute significantly to antimicrobial defence in infectious diseases and to the physiological and pathological consequences of immune complex formation, in short to the benefit and burden of inflammation. These effects depend on the cleavage of low-molecular-weight activation peptides from C4, C3 and C5: the anaphylatoxic peptides or anaphylatoxins C4a, C3a and C5a. The known primary structures1 are given in Table 11.1. Generated from the N-termini of the a-chains of C4, C3 or C5 via activation of the classical or alternative pathways of complement, they interact with specific receptors on a number of cell types of the phagocytic system, mainly granulocytes and monocytes/macrophages. In addition, endothelial cells, possibly some T-cell subsets and, in some species, platelets express anaphylatoxin-receptors. Although the C5a receptor is often expressed with the C3a/C4a receptor, they are distinct species. The ligand-receptor interaction triggers G-protein coupled signal transduction pathways and results in a number of cellular responses2-15, the most significant of which are documented in Table 11.2. Some of these biological effects are in general use as highly sensitive and specific in vitro detection systems for anaphylatoxins, e.g. smooth muscle contraction, enzyme release, stimulation of the respiratory burst, histamine release, ATP release,