Volume 25, No 8, Aug 2015

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 25 Issue 8, August 2015: 893-910   |  Open Access

ORIGINAL ARTICLES

High salt primes a specific activation state of macrophages, M(Na)

Wu-Chang Zhang^1,*, Xiao-Jun Zheng^1,*, Lin-Juan Du^1,*, Jian-Yong Sun¹, Zhu-Xia Shen¹, Chaoji Shi², Shuyang Sun², Zhiyuan Zhang², Xiao-qing Chen³, Mu Qin³, Xu Liu³, Jun Tao⁴, Lijun Jia⁵, Heng-yu Fan⁶, Bin Zhou¹, Ying Yu¹, Hao Ying¹, Lijian Hui⁷, Xiaolong Liu⁷, Xianghua Yi⁸, Xiaojing Liu⁹, Lanjing Zhang^10,11,12,13 and Sheng-Zhong Duan¹

¹Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China
²Shanghai Key Laboratory of Stomatology, Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
³Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
⁴Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
⁵Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China
⁶Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China
⁷State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
⁸Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
⁹Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
¹⁰Department of Pathology, University Medical Center of Princeton, Plainsboro, NJ, USA
¹¹Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA
¹²Department of Pathology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA
¹³Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ 08854-8020, USA Correspondence: Sheng-Zhong Duan, Tel/Fax: +86-21-5492-0981(szduan@sibs.ac.cn)

High salt is positively associated with the risk of many diseases. However, little is known about the mechanisms. Here we showed that high salt increased proinflammatory molecules, while decreased anti-inflammatory and proendocytic molecules in both human and mouse macrophages. High salt also potentiated lipopolysaccharide-induced macrophage activation and suppressed interleukin 4-induced macrophage activation. High salt induced the proinflammatory aspects by activating p38/cFos and/or Erk1/2/cFos pathways, while inhibited the anti-inflammatory and proendocytic aspects by Erk1/2/signal transducer and activator of transcription 6 pathway. Consistent with the in vitro results, high-salt diet increased proinflammatory gene expression of mouse alveolar macrophages. In mouse models of acute lung injury, high-salt diet aggravated lipopolysaccharide-induced pulmonary macrophage activation and inflammation in lungs. These results identify a novel macrophage activation state, M(Na), and high salt as a potential environmental risk factor for lung inflammation through the induction of M(Na).

10.1038/cr.2015.87

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