Zheng Xianchong, Chen Mimi, Meng Xiaojing, Chu Xinwei, Cai Chunqing, Zou Fei
Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou, China.
Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou, China.
Mol Immunol. 2017 Jul;87:23-32. doi: 10.1016/j.molimm.2017.03.019. Epub 2017 Apr 4.
During an inflammatory response, polarization of neutrophils is necessary for effective chemotaxis and bacterial endocytosis. Ca uptake into mitochondria through the mitochondrial calcium uniporter (MCU) is crucial for cell metabolism, signaling and survival; however, the physiological role of MCU in human neutrophils remains unclear. Here we show that MCU is vital for the polarization and chemotaxis of neutrophils. Activation of MCU by spermine promotes neutrophil polarization and chemotaxis, whereas inhibition of MCU by Ru360 blunts both processes. We also provide evidence that this role of the MCU in neutrophils may result from modulation of mitochondrial fission by increased levels of pDrp1 S616 via accumulation of Ca into the mitochondrial matrix. Thus, our study identifies the dependence of neutrophil polarization and chemotaxis on the MCU and highlights the importance of regulating mitochondrial fission during the anti-inflammatory cascade in human neutrophils.
在炎症反应过程中，中性粒细胞的极化对于有效的趋化作用和细菌内吞作用是必要的。通过线粒体钙单向转运体（MCU）将钙摄取到线粒体中对于细胞代谢、信号传导和存活至关重要；然而，MCU在人类中性粒细胞中的生理作用仍不清楚。在这里，我们表明MCU对中性粒细胞的极化和趋化作用至关重要。精胺激活MCU可促进中性粒细胞极化和趋化作用，而Ru360抑制MCU则会削弱这两个过程。我们还提供证据表明，MCU在中性粒细胞中的这一作用可能是由于通过钙在线粒体基质中的积累导致pDrp1 S616水平升高从而调节线粒体分裂所致。因此，我们的研究确定了中性粒细胞极化和趋化作用对MCU的依赖性，并强调了在人类中性粒细胞抗炎级联反应过程中调节线粒体分裂的重要性。
