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

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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, Iredale, John P.·2005·Journal of Clinical Investigation

DOI 10.1172/jci200522675PMC PMC539199

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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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Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.
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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.
ORCID: Duffield, Jeremy S.
Forbes, Stuart J.
Lang, Richard
Iredale, John P.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2005-01-03
Volume: 115
Issue: 1
Pages: 56-65
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci200522675
PMC: PMC539199
OpenAlex: W4250007760
Cited by: 1,649
References: 3
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: bronze
doi.org
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 › Surgery › 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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Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair

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