Membrane attack complex (C5b-9) (MAC)

The membrane attack complex (MAC, C5b-9) is a pore-forming protein complex assembled on cell membranes during terminal complement activation. It consists of complement components C5b, C6, C7, C8, and multiple copies of C9, forming a transmembrane ring. MAC assembly starts with C5 cleavage, yielding C5b, which binds sequentially to C6, C7, C8, and then polymerizing C9 molecules. This process results in a large β-barrel channel that disrupts membrane integrity and causes cell lysis––critical for innate host defense against microbes. Sublytic MAC quantities can induce cell proliferation, survival signaling, and immune modulation, contributing to both normal physiology and disease. Excess or misdirected MAC formation is implicated in autoimmune, inflammatory, and tissue-destructive diseases; thus, MAC and its formation are therapeutic targets in these contexts. The soluble form of MAC (sC5b-9) is clinically used as a biomarker for complement activation.

Other names

Membrane attack complexMACTerminal complement complex (TCC)C5b-9 complexSoluble C5b-9 (sC5b-9; refers to the fluid-phase form)

Blockade of C5 cleavage (preventing formation of C5b, and thus MAC) Inhibition or neutralization of MAC or its assembly proteins (prevention of pore formation and cell lysis) Enhancement of MAC clearance (soluble MAC complexes prevented from inserting into host tissues)