Cell Signals Transduced by Complement

The complement system is composed of soluble blood plasma proteins and cell membrane proteins. A major function of the soluble complement proteins is to bind to and destroy invading pathogens. The membrane proteins of the complement system are divided into complement receptors and complement regulatory proteins. Complement receptors on phagocytic cells promote binding and engulfment of pathogens coated with complement opsonins, whereas complement regulatory proteins protect healthy tissues from accidental damage by the soluble complement proteins. Upon binding of complement proteins or protein fragments that are generated during complement activation, these receptors and regulatory proteins transduce various signals into cells bearing them. The complement membrane attack complex C5b-9 binds to cell membranes, independent of any receptor, and also activates multiple signaling pathways. The receptor-dependent and -independent signals transduced by complement components are of great consequence to health and disease. Complement plays an important role in immunoregulation by activating B and T lymphocytes. It may also exert pro- or anti-apoptotic effects on various cell types. At sublytic doses, the complement membrane attack complex has wide-range effects on many cell types leading to cellular responses, such as secretion, adherence, aggregation, chemotaxis and even cell division. Sublytic complement also induces increased cell resistance to lytic doses of complement. Finally, certain pathogens take advantage of complement membrane proteins to gain entry into cells. The emerging data on these complement-related signaling pathways is hereby described.