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.
JCI Insight. 2019 Nov 1;4(21):130508. doi: 10.1172/jci.insight.130508.
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.
炎症可能在高盐摄入与其有害后果之间的联系中发挥作用。然而,目前尚不清楚盐是否会导致人类单核细胞和巨噬细胞的促炎预激。我们通过进行一项随机交叉试验,在 11 名健康人类受试者中进行了为期两周的低盐和高盐饮食,研究了盐对体外和体内单核细胞和巨噬细胞的影响。我们证明盐增加了单核细胞表达趋化因子受体 CCR2,该受体介导炎症性疾病中的单核细胞浸润。与此一致,我们表明盐诱导血浆 MCP-1 增加,单核细胞跨内皮迁移增加,高盐饮食后皮肤巨噬细胞密度增加。盐暴露后巨噬细胞表现出增强的促炎表型的迹象,体外表现为 LPS 诱导的细胞因子分泌 IL-6、TNF 和 IL-10 增加,高盐饮食后皮肤巨噬细胞上 HLA-DR 表达增加和 CD206 表达减少。总之,我们的数据为炎症性单核细胞和巨噬细胞反应作为高盐摄入有害影响的潜在贡献者提供了可能性。