Journal
MOLECULAR IMMUNOLOGY
Volume 87, Issue -, Pages 23-32Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2017.03.019
Keywords
Neutrophil polarization; Inflammation; Mitochondrial fission; Mitochondrial calcium uniporter (MCU); Dynamin-related protein 1 (Drp1)
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Funding
- National Natural Science Foundation of China [81502799]
- Natural Science Foundation of Guangdong Province [2015A030310100]
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During an inflammatory response, polarization of neutrophils is necessary for effective chemotaxis and bacterial endocytosis. Ca2+ uptake into mitochondria through the mitochondria! 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 5616 via accumulation of Ca2+ 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. (C) 2017 Elsevier Ltd. All rights reserved.
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