title: Alternative complement pathway component Factor D contributes to efficient clearance of tissue debris following acute CCl₄-induced injury.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Gail A
authors.initials: GA
authors.lastname: Cresci
authors.affiliation: Department of Pathology Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Allende
authors.affiliation: Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Megan R
authors.initials: MR
authors.lastname: McMullen
authors.affiliation: Department of Gastroenterology, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: nagyL3@ccf.org.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Nagy
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D049109:Cell Proliferation; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology* / Q000473:pathology*; D015922:Complement C1q / Q000172:deficiency; D003176:Complement C3 / Q000378:metabolism; D011416:Complement Factor D / Q000172:deficiency / Q000378:metabolism*; D003170:Complement Pathway, Alternative / Q000276:immunology*; D005260:Female; D022781:Hepatocytes / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D009336:Necrosis; D020556:Neutrophil Infiltration; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D003176:Complement C3; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D015922:Complement C1q; D002251:Carbon Tetrachloride; D011416:Complement Factor D
keywords: Acute liver injury; Alternative pathway; Complement; Factor D; Necrosis