Salt increases monocyte CCR2 expression and inflammatory responses in humans.

Eliane Fe Wenstedt, Sanne Gs Verberk, Jeffrey Kroon, Annette E Neele, Jeroen Baardman, Nike Claessen, Özge T Pasaoglu, Emma Rademaker, Esmee M Schrooten, Rosa D Wouda, Menno Pj de Winther, Jan Aten, Liffert Vogt, Jan Van den Bossche

Journal: JCI insight 2020;4(21):e130508

PMID: 31672939

Abstract

Inflammation may play a role in the link between high salt intake and its deleterious consequences. However, it is unknown whether salt can induce proinflammatory priming of monocytes and macrophages in humans. We investigated the effects of salt on monocytes and macrophages in vitro and in vivo by performing a randomized crossover trial in which 11 healthy human subjects adhered to a 2-week low-salt and high-salt diet. We demonstrate that salt increases monocyte expression of CCR2, a chemokine receptor that mediates monocyte infiltration in inflammatory diseases. In line with this, we show a salt-induced increase of plasma MCP-1, transendothelial migration of monocytes, and skin macrophage density after high-salt diet. Macrophages demonstrate signs of an increased proinflammatory phenotype after salt exposure, as represented by boosted LPS-induced cytokine secretion of IL-6, TNF, and IL-10 in vitro, and by increased HLA-DR expression and decreased CD206 expression on skin macrophages after high-salt diet. Taken together, our data open up the possibility for inflammatory monocyte and macrophage responses as potential contributors to the deleterious effects of high salt intake.

Address: Amsterdam UMC, University of Amsterdam, Department of Internal Medicine, Section of Nephrology, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands.; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, Amsterdam, Netherlands.; Amsterdam UMC, University of Amsterdam, Department of Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands.; Amsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Section of Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands.; Amsterdam UMC, University of Amsterdam, Department of Pathology, Amsterdam, Netherlands.; Amsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Section of Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands.; Institute for Cardiovascular Prevention (IPEK), Munich, Germany.; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, Amsterdam, Netherlands.; Amsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Section of Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands.
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