Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
FASEB J. 2011 Dec;25(12):4358-68. doi: 10.1096/fj.11-190587. Epub 2011 Sep 1.
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.
尽管 AMPK 在调节能量平衡方面发挥着重要作用，但最近的研究表明，AMPK 的激活具有很强的抗炎作用。在本实验中，我们研究了 AMPK 在吞噬作用中的作用。我们发现，巨噬细胞摄取大肠杆菌或凋亡细胞会增加 AMPK 活性。AMPK 激活增加了中性粒细胞或巨噬细胞摄取细菌的能力（分别增加了 46±7.8%和 85±26%，与对照组相比，P<0.05），并增加了巨噬细胞摄取凋亡细胞的能力（增加了 21±1.4%，与对照组相比，P<0.05）。AMPK 激活导致细胞骨架重新排列，包括增强肌动蛋白和微管网络的形成。Rac1 的下游效应物 PAK1/2 和 WAVE2 的激活伴随着 AMPK 的激活。AMPK 激活还诱导参与微管合成的 CLIP-170 蛋白的磷酸化。吞噬作用的增加可被特定的 AMPK 抑制剂化合物 C、AMPKα1 的 siRNA、Rac1 抑制剂或破坏肌动蛋白或微管网络的试剂逆转。在体内，AMPK 激活使肺部细菌的吞噬作用增加了 75±5%，与对照组相比（P<0.05）。这些结果表明 AMPK 在增强中性粒细胞和巨噬细胞的吞噬活性方面具有新的功能。
