Figure 4.

The complement system cascades and possible intervention options. The complement system is activated by the classical, the lectin, or the alternative pathway. All pathways have in common that they lead to the formation of C3 and C5, which in turn leads to the emergence of the membrane attack complex (MAC), which forms a pore in cell membranes, leading to the lysis of the affected cell. C3 is hydrolyzed to C3b and C3a. C3 and C5 represent opportunities to inhibit MAC formation. C3 can be inhibited by overexpression of the specifically designed protein C2-Crry. C5 can be inhibited by monoclonal antibodies. In addition to the universal proteins C3 and C5, C1q also offers the possibility for therapeutic intervention. Gene knockout of C1qa leads to reduced MAC formation. SERPING1, in turn, can inhibit C1r and C1s in a cellular naturally occurring process. The complement system is activated by several stimuli, one being the formation of the HMGB1-C1q complex which initiates the formation of C4, C2, and the MAC. This can be prevented by a neutralizing anti-HMGB1 antibody. The graphic was created by BioRender.com. The copyright was gained from Biorender.com (accessed·on 31 October 2021).