Alternative complement pathway component Factor D contributes to efficient clearance of tissue debris following acute CCl4-induced injury

• Published in: Molecular immunology 2015-03, Vol.64 (1), p.9-17
• Main Authors: Cresci, Gail A., Allende, Daniela, McMullen, Megan R., Nagy, Laura E.
• Format: Article
• Language: English
• Subjects: Acute liver injury; Alternative pathway; Animals; Carbon Tetrachloride; Cell Proliferation; Chemical and Drug Induced Liver Injury - immunology; Chemical and Drug Induced Liver Injury - pathology; Complement; Complement C1q - deficiency; Complement C3 - metabolism; Complement Factor D - deficiency; Complement Factor D - metabolism; Complement Pathway, Alternative - immunology; Factor D; Female; Hepatocytes - pathology; Inflammation - pathology; Interleukin-6 - metabolism; Liver - immunology; Liver - pathology; Mice, Inbred C57BL; Necrosis; Neutrophil Infiltration; Phosphorylation; STAT3 Transcription Factor - metabolism
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2014.10.017

•We examine which complement activation pathway is involved for timely liver recovery following an acute toxic injury.•We utilized mice deficient in C1qa, C4 and Factor D, lacking the classical, classical/MBL, and alternative pathways of complement activation.•Factor D-deficient mice had worse liver injury compared to other genotypes.•Factor D-deficient mice were unable to adequately clear injured tissue.•We demonstrate the importance of the alternative complement pathway in facilitating opsonization of damaged tissue for a timely reparative process following an acute toxic liver injury. Complement, part of the innate immune system, is involved with immune protection against invading pathogens as well as cell survival and tissue regeneration. It is known that complement activation is required for timely hepatocyte recovery following an acute toxic injury, but which pathway of complement activation is involved in response to hepatocyte injury has not been identified. In these studies we utilize mice deficient in C1qa, C4 and Factor D, lacking the classical, classical/MBL, and alternative pathways of complement activation, respectively, to identify an essential role for Factor D in the ability of the liver to recover from acute toxic injury. Here we demonstrate that following an acute CCl4-induced injury, the involvement of the alternative complement pathway is essential for efficient liver recovery.