Inhibition of Complement in the Membrane Attack Pathway

Abstract

The terminal or membrane attack pathway represents the final common pathway for both the classical and alternative activation pathways of complement. The membrane attack pathway differs from the activation pathways in that it is not a proteolytic cascade (1,2). Assembly of the membrane attack complex (MAC) involves the sequential assembly of the five terminal complement proteins into a heteropolymeric complex. Cleavage of C5 by the enzymes of the classical or alternative pathways is the final enzymatic step and can be considered to be either the final step in the activation pathway or the first step in the membrane attack pathway. For the purposes of this Chapter, I will take the latter stance. The small (10 kDa) fragment released from C5 following cleavage, C5a, is a powerful chemotactic and anaphylactic agent that binds specific receptors on phagocytes and other cell types and triggers important activation events.