Membrane attack complex (MAC) (MAC)

The Membrane Attack Complex (MAC), also known as C5b-9, is a multi-protein assembly of the innate immune system's complement cascade (StatPearls, 2023). It is formed by the sequential binding of complement components C5b, C6, C7, C8, and multiple C9 molecules, creating a transmembrane pore in the target cell membrane (UniProt, 2024). This pore leads to osmotic lysis and cell death, primarily serving to eliminate Gram-negative bacteria and other pathogens (PubMed, 2021). However, dysregulation of MAC formation can lead to the destruction of host cells, contributing to various autoimmune and inflammatory diseases such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) (NIH, 2023). Therapeutic strategies often focus on inhibiting C5 cleavage to prevent the initiation of MAC assembly, thereby protecting host tissues from complement-mediated damage (FDA, 2024). Because the MAC is essential for defense against Neisseria species, drugs targeting this complex carry a significant risk of predisposing patients to life-threatening meningococcal infections.

Other names

C5b-9 complexTerminal complement complexTCCComplement C5b-9Membrane attack complex

Inhibition of C5 cleavage to prevent C5b formation and subsequent MAC assembly; direct binding to C5 to block its interaction with C5 convertase (FDA, 2024).