Figure 7.

High-mobility group box 1 (HMGB1)-induced complement activation model. HMGB1 protein is actively secreted or passively released by stress injury on cells or organs in the forms of three different redox statuses, which may differently modulate immunological activities. Extracellular HMGB1 can activate the classical pathway of complement system in an antibody (Ab)-independent manner after binding to C1q, resulting in forming C5b-9 membrane attack complexes (MAC) where HMGB1 is accumulated. Thus, HMGB1-induced complement activation is proposed to be able to exacerbate sterile inflammation.