title: AMP-activated protein kinase enhances the phagocytic ability of macrophages and neutrophils.
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.
authors: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: Hong-Beom
authors: HB
authors: Bae
authors: Jaroslaw W
authors: JW
authors: Zmijewski
authors: Jessy S
authors: JS
authors: Deshane
authors: Jean-Marc
authors: JM
authors: Tadie
authors: David D
authors: DD
authors: Chaplin
authors: Seiji
authors: S
authors: Takashima
authors: Edward
authors: E
authors: Abraham
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D066298:In Vitro Techniques; D008264:Macrophages / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology* / Q000648:ultrastructure; D010587:Phagocytosis / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism; D054462:p21-Activated Kinases / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein
chemical_list: D000199:Actins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009479:Neuropeptides; D034741:RNA, Small Interfering; C484602:Rac1 protein, mouse; C492303:Wasf2 protein, mouse; D051300:Wiskott-Aldrich Syndrome Protein Family; C076744:cytoplasmic linker protein 170; C548179:Prkaa1 protein, mouse; C515905:Pak1 protein, mouse; C515909:Pak2 protein, mouse; D054462:p21-Activated Kinases; D055372:AMP-Activated Protein Kinases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein