Cited by 1,649Liver physiology and pathologyWound Healing and TreatmentsCardiac Fibrosis and Remodeling

Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair

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Duffield, Jeremy S., Forbes, Stuart J., Constandinou, Christothea M., Clay, Spike, Partolina, Marina, Vuthoori, Srilatha, Wu, Shengji, Lang, Richard +1 more·2005·Journal of Clinical Investigation

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.

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Crossref · 10.1172/jci200522675

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Authors
Duffield, J. S., Forbes, S. J., Constandinou, C. M., Clay, S., Partolina, M., Vuthoori, S., Wu, S., Lang, R., & Iredale, J. P.
Affiliations
  • Brigham and Women's Hospital (US)
  • St Mary's Hospital (GB)
  • University of Southampton (GB)
  • Centre for Inflammation Research (GB)
  • New York University (US)
  • Regeneron (United States) (US)
  • Cincinnati Children's Hospital Medical Center (US)
Corresponding author
Duffield, Jeremy S.
Venue
Journal of Clinical Investigation
Published
2005-01-03
Volume
115
Issue
1
Pages
56-65
ISSN
0021-9738 (ISSN-L)
OpenAlex
W4250007760
Cited by
1,649
References
2
Citations by year
2026: 40 · 2025: 58 · 2024: 84 · 2023: 66 · 2022: 79 · 2021: 97 · 2020: 81 · 2019: 96 · 2018: 87 · 2017: 90 · 2016: 100 · 2015: 98 · 2014: 95 · 2013: 92 · 2012: 100
FWCI
39.61
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Funders
  • Wellcome Trust
  • Children's Liver Disease Foundation
  • Imperial College London
  • Wessex Medical Research
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
macrophages, liver fibrosis, myofibroblasts, extracellular matrix degradation, macrophage heterogeneity, carbon tetrachloride
MeSH terms
Animals, Carbon Tetrachloride, Diphtheria Toxin, Extracellular Matrix, Female, Gene Expression Regulation, Liver, Liver Cirrhosis, Macrophages, Mice, Transgenic, Models, Biological, Wound Healing, Cytokines, Gene Deletion, CD11b Antigen, Mice

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