title: Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair.
abstract: Macrophages perform both injury-inducing and repair-promoting tasks in different models of inflammation, leading to a model of macrophage function in which distinct patterns of activation have been proposed. We investigated macrophage function mechanistically in a reversible model of liver injury in which the injury and recovery phases are distinct. Carbon tetrachloride---induced liver fibrosis revealed scar-associated macrophages that persisted throughout recovery. A transgenic mouse (CD11b-DTR) was generated in which macrophages could be selectively depleted. Macrophage depletion when liver fibrosis was advanced resulted in reduced scarring and fewer myofibroblasts. Macrophage depletion during recovery, by contrast, led to a failure of matrix degradation. These data provide the first clear evidence that functionally distinct subpopulations of macrophages exist in the same tissue and that these macrophages play critical roles in both the injury and recovery phases of inflammatory scarring.
authors.affiliation: Medical Research Council Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom. jduffield@rics.bwh.harvard.edu
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Duffield
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Forbes
authors.forename: Christothea M
authors.initials: CM
authors.lastname: Constandinou
authors.forename: Spike
authors.initials: S
authors.lastname: Clay
authors.forename: Marina
authors.initials: M
authors.lastname: Partolina
authors.forename: Srilatha
authors.initials: S
authors.lastname: Vuthoori
authors.forename: Shengji
authors.initials: S
authors.lastname: Wu
authors.forename: Richard
authors.initials: R
authors.lastname: Lang
authors.forename: John P
authors.initials: JP
authors.lastname: Iredale
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics; D004167:Diphtheria Toxin / Q000633:toxicity; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D008099:Liver / Q000293:injuries / Q000378:metabolism* / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D014945:Wound Healing
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D004167:Diphtheria Toxin; D002251:Carbon Tetrachloride