The Role of Decay Accelerating Factor in Environmentally Induced and Idiopathic Systemic Autoimmune Disease

Figure 1

Overview of the complement system. Stimulated by antigen : antibody complexes, bacterial cell surfaces, and spontaneous hydrolysis, respectively, the classical, lectin, and alternative pathways converge to convert C3 to C3 convertase, an enzyme capable of initiating a cascade that results in cell membrane pore formation and subsequent cell lysis known as the membrane attack complex (MAC). To protect host cells from complement activation four main plasma membrane complement regulatory proteins are expressed, CD59 (membrane inhibitor of reactive lysis (MIRL)), CD35 (type 1 complement receptor (CR1)), CD46 (membrane cofactor protein, (MCP)), and CD55 (decay accelerating factor (DAF)), that interrupt the complement cascade on self-cells. CD59 blocks MAC complex formation, CD35 acts as a cofactor to inactivate C3b and C4b by factor I, and interacts with C3b and C4b to promote immune-complex removal, CD46 acts as a cofactor to inactivate C3b and C4b through factor I and DAF inhibits the cleavage of C3 and C5 by blocking the formation of C3 and C5 convertases and accelerating their decay. MBL: mannose-binding lectin; MASPs: MBL-associated serine proteases; PAMP: pathogen-associated molecular pattern; Fb: factor B.