Functional plasticity of macrophages: reversible adaptation to changing microenvironments
Open accessAbstract
There has been substantial research activity in the past decade directed at phenotyping macrophage lineages and defining macrophage functional subsets or patterns of activity. The emphasis over the past 2–3 years has been to divide macrophage functional patterns into type 1 (Th1-driven) or type 2 (Th2-driven) functions. However, a huge array of environmental factors (including cytokines, chemokines, pattern recognition receptors, hormones) differentially regulates macrophage response patterns, resulting in the display of numerous distinct, functional phenotypes. Upon stimulation, a macrophage does not display just a single set of functions but rather displays a progression of functional changes in response to the progressive changes in its microenvironment. The remarkable ability of monocytes and tissue macrophages to adapt to changes in their microenvironment challenges the thesis that macrophages displaying unique tissue-specific or response-specific, functional patterns represent distinct lineages. With the exception of mature osteoclasts and mature dendritic cells, evidence supporting stable differentiation as the basis for macrophage functionl heterogeneity is equivocal. The concept of whether macrophages develop into functional subsets as opposed to continuously adapting their functional pattern in response to the changing environment of a progressive inflammatory response is important to resolve from the perspectives of therapeutic targeting and understanding the role of macrophages in disease pathogenesis.
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Macrophages switch polarization states in response to their microenvironment.
“Unlike terminally differentiated cells, macrophages switch polarization states in response to their microenvironment.This is emphasized by the contrasting gene expression during early and late stages of the FBR [24], as well as their ability to adapt functionality in response to the temporal presentation of stimuli [25].”
From Biomaterial based modulation of macrophage polarization: a review and suggested design principles (2015) · cites this paper as [25]
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- Authors
- Stout, R. D., & Suttles, J.
- Affiliations
- University of Louisville (US)
- Corresponding author
- Stout, Robert D
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-06-24
- Volume
- 76
- Issue
- 3
- Pages
- 509-513
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- PMC
- PMC1201486
- OpenAlex
- W2165365415
- Cited by
- 751
- References
- 27
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 25 · 2023: 26 · 2022: 27 · 2021: 28 · 2020: 29 · 2019: 36 · 2018: 35 · 2017: 38 · 2016: 28 · 2015: 42 · 2014: 58 · 2013: 52 · 2012: 54
- FWCI
- 8.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute for Aging
- Kentucky Lung Cancer Research Fund
- National Institute of Allergy and Infectious Disease
- National Multiple Sclerosis Society
- Arthritis Foundation
- Commonwealth of Kentucky Research Challenge Trust Fund
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- macrophage heterogeneity, Th1/Th2 immune response, monocytes, tissue macrophages, cytokines, chemokines, pattern recognition receptors, macrophage differentiation, inflammation
- MeSH terms
- Adaptation, Physiological, Animals, Cell Differentiation, Chemotaxis, Leukocyte, Humans, Immunologic Surveillance, Inflammation, Macrophages, Phenotype, Cytokines, Receptors, Cytokine
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