Fig. 8.

Complement activation and involvement during alcoholic liver disease. In mouse models of ALD, ethanol (EtOH) induces the activation of complement via complement component 1, Q subcomponent (C1q), leading to the cleavage of complement protein 3 (C3) into the anaphylatoxin fragment of C3 (C3a) and C3b. The potent anaphylatoxins C3a and C5a act on cognate receptors (C3aR and C5aR) on resident hepatic macrophages (Kupffer cells) to initiate the transcription of proinflammatory mediators. During chronic EtOH, amplification of complement via the alternative pathway is required to provide essential opsonins (C3b/iC3b/C3c) on the surface of damaged cells in the liver, facilitating clearance of debris and allowing for resolution and repair. TNF-α, tumor necrosis factor-α; IL-6, interleukin-6; MCP-1, macrophage chemoattractant protein-1; FB, complement factor B; FD, complement factor D; C4, complement protein 4; C2, complement protein 2; C4b, 2a, C3 convertase; fBb, FB activation fragment b; fBa, FB activation fragment a. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2018. All Rights Reserved.