title: Association of age-dependent liver injury and fibrosis with immune cell populations.
abstract: OBJECTIVE
  The liver's response to injury is fibrosis, and when chronic, cirrhosis. Age is a critical factor impacting many immune-mediated processes, potentially including the liver's wounding response to injury.
  
  
  METHODS
  The effects of age on acute and chronic liver injury were evaluated using a carbon tetrachloride model in mice. Lymphocyte and macrophage populations were assessed by flow cytometry and immunohistochemical analysis.
  
  
  RESULTS
  Acute liver injury was greater in 18-month-old (old) mice than in 9-month-old (middle-aged) mice as judged by changes in aminotransferases. Similarly, livers of 18-month-old mice had a significantly greater fibrogenic response to injury than did livers of 9-month-old mice after chronic injury (assessed by col1α1 mRNA expression, morphometric analysis and hydroxyproline measurement). Interestingly, livers from young mice (6 weeks old) also exhibited an increase in fibrogenesis compared to 9-month-old mice, albeit not to the same degree as in old mice. Consistent with a role for macrophages in fibrogenesis, the number of liver macrophages in young and 9-month-old mice increased, while in chronically injured livers of 18-month-old mice, the number of macrophages was reduced, and was less than in the livers of young and 9-month-old injured livers.
  
  
  CONCLUSIONS
  Our data indicate that the fibrogenic response to injury varies substantially with age, and moreover that macrophage recruitment and dynamics may be an important component in differential age-associated fibrotic disease.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC, USA.
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Collins
authors.forename: Zoie E
authors.initials: ZE
authors.lastname: Holzknecht
authors.forename: Kellie A
authors.initials: KA
authors.lastname: Lynn
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sempowski
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Smith
authors.forename: Songling
authors.initials: S
authors.lastname: Liu
authors.forename: William
authors.initials: W
authors.lastname: Parker
authors.forename: Don C
authors.initials: DC
authors.lastname: Rockey
mesh_terms: D000367:Age Factors; D000375:Aging / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016207:Cytokines; D005353:Fibronectins; D012333:RNA, Messenger; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase; D006909:Hydroxyproline
keywords: aminotransferase; cirrhosis; collagen; extracellular matrix; smooth muscle actin