Mechanisms of Organ Injury and Repair by Macrophages
Open accessAbstract
Macrophages regulate tissue regeneration following injury. They can worsen tissue injury by producing reactive oxygen species and other toxic mediators that disrupt cell metabolism, induce apoptosis, and exacerbate ischemic injury. However, they also produce a variety of growth factors, such as IGF-1, VEGF-α, TGF-β, and Wnt proteins that regulate epithelial and endothelial cell proliferation, myofibroblast activation, stem and tissue progenitor cell differentiation, and angiogenesis. Proresolving macrophages in turn restore tissue homeostasis by functioning as anti-inflammatory cells, and macrophage-derived matrix metalloproteinases regulate fibrin and collagen turnover. However, dysregulated macrophage function impairs wound healing and contributes to the development of fibrosis. Consequently, the mechanisms that regulate these different macrophage activation states have become active areas of research. In this review, we discuss the common and unique mechanisms by which macrophages instruct tissue repair in the liver, nervous system, heart, lung, skeletal muscle, and intestine and illustrate how macrophages might be exploited therapeutically.
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The relative quantification of CD68 and CD163 proteins roughly distinguishes the activation of M1 and M2 macrophages.
“The relative quantification of CD68 and CD163 proteins roughly distinguishes the activation of M1 and M2 macrophages (Vannella and Wynn, 2017;Huang et al., 2018;Kim et al., 2019).”
From Nanosilver alleviates foreign body reaction and facilitates wound repair by regulating macrophage polarization (2023) · cites this paper as Vannella and Wynn, 2017
In “Polarizing Toward Repair” (page not provided), the paper mentions CD68-positive macrophages but does not identify CD68 as an M1 marker; it describes the protective macrophages as neither M(IFN-γ)- nor M(IL-4)-like. Searches for CD163 and for relative CD68/CD163 quantification found no passage establishing that the two proteins distinguish M1 from M2 activation. (LLM, conf=0.76)
Experimental — accuracy not yet measuredPro-fibrotic macrophages commonly coordinate scar formation via interactions with fibroblasts, the major cellular source of pathological extracellular matrix deposition during fibrosis.
“pro-fibrotic macrophages commonly coordinate scar formation via a range of interactions with fibroblasts, the major cellular source of pathological extracellular matrix deposition during fibrosis18,27,74–78.”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [77]
Proximity is crucial for crosstalk between macrophages and contractile fibroblasts.
“Previous work has shown that proximity is crucial to allow crosstalk between macrophages and contractile fibroblasts27,77,78”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [77]
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- Authors
- Vannella, K. M., & Wynn, T. A.
- Affiliations
- National Institutes of Health (US)
- Venue
- Annual Review of Physiology
- Publisher
- Annual Reviews
- Published
- 2017-02-10
- Volume
- 79
- Issue
- 1
- Pages
- 593-617
- ISSN
- 0066-4278 (ISSN-L)
- 1545-1585
- OpenAlex
- W2467677013
- Semantic Scholar
- 00554bdce4ebdeef31bcb674e3634efc26188db4
- Cited by
- 656
- References
- 127
- Citations by year
- 2026: 52 · 2025: 76 · 2024: 102 · 2023: 78 · 2022: 89 · 2021: 73 · 2020: 66 · 2019: 60 · 2018: 41 · 2017: 19
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- macrophages, tissue repair, tissue regeneration, wound healing, macrophage polarization, reactive oxygen species, apoptosis, growth factors, angiogenesis, myofibroblast activation, matrix metalloproteinases, fibrosis, liver, nervous system, heart, lung, skeletal muscle, intestine, anti-inflammatory macrophages
- MeSH terms
- Animals, Cell Differentiation, Homeostasis, Humans, Macrophages, Regeneration, Wound Healing
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