Figure 1

Schematic drawing of complement activation pathways, immunological functions, and specific inhibitory strategies used in experimental head injury models. Complement is activated either through the classical, lectin, or alternative pathways. Activation of complement leads to the formation of multi-molecular enzyme complexes termed convertases that cleave C3 and C5, the central proteins of the complement system. The proteolytic fragments generated by cleavage of C3 and C5 mediate most of the biological activities of complement. C3b, and proteolytic fragments generated from C3b, are important opsonins that target pathogens for removal by phagocytic cells via complement receptors specific for these proteins. These molecules have furthermore been shown to bridge innate to adaptive immune responses by the activation of B-cells. C3a and C5a are potent anaphylatoxins with chemotactic and inflammatory properties. Generation of C5b by cleavage of C5 initiates the formation of the membrane attack complex (MAC, C5b-9) through the terminal complement pathway. The MAC forms through the self-association of C5b along with C6 through C9 and leads to the formation of a large membranolytic complex capable of lysing cells. Therapeutic modalities from experimental head injury models are aimed either at blocking specific activation pathways (classical, alternative), components (C5) and proteolytic fragments (C5a, C5aR), or by a "pan"-inhibition of C3 convertases, leading to a complete shut-down of complement activation. See text for references and explanations. C1-Inh, C1-inhibitor; C5aR, anaphylatoxin C5a receptor (CD88); Crry-Ig, Complement receptor type 1-related protein y, IgG1-linked murine recombinant fusion protein; MBP, mannose-binding protein; rVCP, recombinant Vaccinia virus complement control protein; sCR1, soluble complement receptor type 1.