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Updated: May 29, 2026
Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
AMP-activated protein kinase enhances the phagocytic ability of macrophages and neutrophils
Hong-Beom Bae1, Jaroslaw W Zmijewski, Jessy S Deshane
1Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Abstract:
Although AMPK plays well-established roles in the modulation of energy balance, recent studies have shown that AMPK activation has potent anti-inflammatory effects. In the present experiments, we examined the role of AMPK in phagocytosis. We found that ingestion of Escherichia coli or apoptotic cells by macrophages increased AMPK activity. AMPK activation increased the ability of neutrophils or macrophages to ingest bacteria (by 46 ± 7.8 or 85 ± 26%, respectively, compared to control, P<0.05) and the ability of macrophages to ingest apoptotic cells (by 21 ± 1.4%, P<0.05 compared to control). AMPK activation resulted in cytoskeletal reorganization, including enhanced formation of actin and microtubule networks. Activation of PAK1/2 and WAVE2, which are downstream effectors of Rac1, accompanied AMPK activation. AMPK activation also induced phosphorylation of CLIP-170, a protein that participates in microtubule synthesis. The increase in phagocytosis was reversible by the specific AMPK inhibitor compound C, siRNA to AMPKα1, Rac1 inhibitors, or agents that disrupt actin or microtubule networks. In vivo, AMPK activation resulted in enhanced phagocytosis of bacteria in the lungs by 75 ± 5% vs. control (P<0.05). These results demonstrate a novel function for AMPK in enhancing the phagocytic activity of neutrophils and macrophages.
Insights
AMPK activation enhances phagocytosis in immune cells like neutrophils and macrophages. This process involves cytoskeletal changes and is crucial for clearing bacteria and apoptotic cells.
Area of Science:
- Immunology
- Cell Biology
- Metabolism
Background:
- AMP-activated protein kinase (AMPK) is known for regulating energy balance.
- Emerging evidence highlights AMPK's anti-inflammatory properties.
- Its role in phagocytosis, a key immune process, remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of AMPK in the phagocytic activity of neutrophils and macrophages.
- To understand the molecular mechanisms underlying AMPK-mediated enhancement of phagocytosis.
Main Methods:
- Assessed phagocytosis of Escherichia coli and apoptotic cells by neutrophils and macrophages.
- Measured AMPK activity following phagocytic challenges.
- Analyzed cytoskeletal reorganization (actin, microtubules) and downstream signaling pathways (PAK1/2, WAVE2, CLIP-170 phosphorylation).
- Utilized AMPK inhibitors, siRNA, Rac1 inhibitors, and cytoskeletal disruptors to confirm findings.
- Evaluated phagocytosis in vivo in a mouse lung infection model.
Main Results:
- Phagocytosis of bacteria and apoptotic cells increased AMPK activity in macrophages.
- AMPK activation significantly enhanced bacterial and apoptotic cell uptake by neutrophils and macrophages (46-85% increase).
- AMPK activation promoted actin and microtubule network formation, involving Rac1 effectors and CLIP-170 phosphorylation.
- Inhibition of AMPK or disruption of cytoskeletal components reversed the enhanced phagocytosis.
- In vivo studies showed a 75% increase in bacterial phagocytosis in the lungs upon AMPK activation.
Conclusions:
- AMPK plays a novel and significant role in enhancing phagocytic capacity in neutrophils and macrophages.
- AMPK-mediated phagocytosis involves cytoskeletal remodeling and specific signaling pathways.
- Targeting AMPK may represent a therapeutic strategy to boost innate immune responses against pathogens and cellular debris.
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