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Updated: Apr 1, 2026
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
Contribution of metabolic reprogramming to macrophage plasticity and function
Karim C El Kasmi1, Kurt R Stenmark2
1University of Colorado Denver, School of Medicine, Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Aurora, CO, USA.
Abstract:
Macrophages display a spectrum of functional activation phenotypes depending on the composition of the microenvironment they reside in, including type of tissue/organ and character of injurious challenge they are exposed to. Our understanding of how macrophage plasticity is regulated by the local microenvironment is still limited. Here we review and discuss the recent literature regarding the contribution of cellular metabolic pathways to the ability of the macrophage to sense the microenvironment and to alter its function. We propose that distinct alterations in the microenvironment induce a spectrum of inducible and reversible metabolic programs that might form the basis of the inducible and reversible spectrum of functional macrophage activation/polarization phenotypes. We highlight that metabolic pathways in the bidirectional communication between macrophages and stromals cells are an important component of chronic inflammatory conditions. Recent work demonstrates that inflammatory macrophage activation is tightly associated with metabolic reprogramming to aerobic glycolysis, an altered TCA cycle, and reduced mitochondrial respiration. We review cytosolic and mitochondrial mechanisms that promote initiation and maintenance of macrophage activation as they relate to increased aerobic glycolysis and highlight potential pathways through which anti-inflammatory IL-10 could promote macrophage deactivation. Finally, we propose that in addition to their role in energy generation and regulation of apoptosis, mitochondria reprogram their metabolism to also participate in regulating macrophage activation and plasticity.
Insights
Cellular metabolism dictates macrophage plasticity, enabling them to adapt to their microenvironment. Metabolic reprogramming, particularly aerobic glycolysis, drives inflammatory macrophage activation and influences chronic inflammatory conditions.
Area of Science:
- Immunology
- Cell Biology
- Metabolic Pathways
Background:
- Macrophages exhibit diverse functional phenotypes influenced by their microenvironment.
- Macrophage plasticity, or their ability to change function, is critical in various physiological and pathological conditions.
- The precise mechanisms by which the microenvironment regulates macrophage plasticity remain incompletely understood.
Purpose of the Study:
- To review and discuss the role of cellular metabolic pathways in macrophage sensing of the microenvironment.
- To explore how metabolic reprogramming contributes to macrophage functional activation and polarization.
- To highlight the link between macrophage metabolism and chronic inflammatory diseases.
Main Methods:
- Literature review of recent studies on macrophage biology and metabolism.
- Analysis of cellular metabolic pathways involved in macrophage activation and deactivation.
- Discussion of cytosolic and mitochondrial mechanisms regulating macrophage plasticity.
Main Results:
- Distinct microenvironmental alterations induce specific, reversible metabolic programs in macrophages.
- Inflammatory macrophage activation is strongly associated with metabolic reprogramming, including aerobic glycolysis and altered mitochondrial respiration.
- Bidirectional communication between macrophages and stromal cells involves metabolic pathways crucial for chronic inflammation.
Conclusions:
- Cellular metabolic pathways are fundamental to how macrophages sense and respond to their microenvironment, underpinning their plasticity.
- Metabolic reprogramming, particularly aerobic glycolysis, is a key feature of inflammatory macrophage activation.
- Mitochondria play a dynamic role in regulating macrophage activation and plasticity beyond energy production and apoptosis control.
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