title: Variation in dietary salt intake induces coordinated dynamics of monocyte subsets and monocyte-platelet aggregates in humans: implications in end organ inflammation.
abstract: BACKGROUND
  Monocyte activation and tissue infiltration are quantitatively associated with high-salt intake induced target organ inflammation. We hypothesized that high-salt challenge would induce the expansion of CD14++CD16+ monocytes, one of the three monocyte subsets with a pro-inflammatory phenotype, that is associated with target organ inflammation in humans.
  
  
  RESULTS
  A dietary intervention study was performed in 20 healthy volunteers, starting with a 3-day usual diet and followed with a 7-day high-salt diet (≥15 g NaCl/day), and a 7-day low-salt diet (≤5 g NaCl/day). The amounts of three monocyte subsets ("classical" CD14++CD16-, "intermediate" CD14++CD16+ and "non-classical" CD14+CD16++) and their associations with monocyte-platelet aggregates (MPAs) were measured by flow cytometry. Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) was used to evaluate renal hypoxia. Switching to a high-salt diet resulted in CD14++ monocyte activation and a rapid expansion of CD14++CD16+ subset and MPAs, with a reciprocal decrease in the percentages of CD14++CD16- and CD14+CD16++ subsets. In vitro study using purified CD14++ monocytes revealed that elevation in extracellular [Na(+)] could lead to CD14++CD16+ expansion via a ROS dependent manner. In addition, high-salt intake was associated with progressive hypoxia in the renal medulla (increased R2* signal) and enhanced urinary monocyte chemoattractant protein-1 (MCP-1) excretion, indicating a temporal and spatial correlation between CD14++CD16+ subset and renal inflammation. The above changes could be completely reversed by a low-salt diet, whereas blood pressure levels remained unchanged during dietary intervention.
  
  
  CONCLUSIONS
  The present work demonstrates that short-term increases in dietary salt intake could induce the expansion of CD14++CD16+ monocytes, as well as an elevation of MPAs, which might be the underlying cellular basis of high-salt induced end organ inflammation and potential thromboembolic risk. In addition, this process seems largely unrelated to changes in blood pressure levels. This finding provides novel links between dietary salt intake, innate immunity and end organ inflammation.
authors.affiliation: Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Ji
authors.forename: Fei
authors.initials: F
authors.lastname: Yuan
authors.forename: Zhao-Zeng
authors.initials: ZZ
authors.lastname: Guo
authors.forename: Bo
authors.initials: B
authors.lastname: Pang
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Zhang
authors.forename: Tie-Min
authors.initials: TM
authors.lastname: Jiang
authors.forename: Zhuoli
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Li
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001774:Blood Chemical Analysis; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D001794:Blood Pressure; D002448:Cell Adhesion; D002450:Cell Communication / Q000276:immunology; D003404:Creatinine / Q000652:urine; D004032:Diet; D020869:Gene Expression Profiling; D006339:Heart Rate; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress; D010101:Oxygen Consumption; D017382:Reactive Oxygen Species / Q000378:metabolism; D012079:Renal Circulation; D017673:Sodium Chloride, Dietary
chemical_list: D015703:Antigens, CD; D017382:Reactive Oxygen Species; D017673:Sodium Chloride, Dietary; D003404:Creatinine