Role of the human C8 subunits in complement-mediated bacterial killing: evidence that C8γ is not essential

Human C8 is one of five complement components (C5b, C6, C7, C8 and C9) that interact to form the cytolytic membrane attack complex (MAC) on bacterial cell membranes. It is an oligomeric protein composed of a disulfide-linked C8α–γ heterodimer and a non-covalently associated C8β chain. Previous studies revealed that C8α and C8β have distinct roles in the formation of the MAC on simple cells such as erythrocytes and that both subunits are essential for cell lysis. These studies also determined that C8γ is not required for expression of MAC hemolytic activity. To determine if these conclusions are applicable to more biologically relevant systems, the C8 subunits were examined for their ability to support complement-mediated killing of Gram-negative bacteria. Results indicate: (1) C8α–γ, C8α, C8β and C8γ have no independent bactericidal activity; (2) bacterial killing requires C8β and either C8α–γ or C8α; (3) C8α is an effective substitute for C8α–γ in bacterial killing; and (4) C8γ enhances, but is not required for C8 bactericidal activity. Together, these data suggest that C8α and C8β have correspondingly similar roles in MAC-mediated lysis of erythrocytes and bacterial killing. Furthermore, they provide the first direct evidence that C8γ is not required for complement-mediated killing of Gram-negative bacteria.