Sodium activates human monocytes via the NADPH oxidase and isolevuglandin formation.
Sodium activates human monocytes via the NADPH oxidase and isolevuglandin formation.
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DOI：
10.1093/cvr/cvaa207
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发表时间：
2021-04-23
影响因子：
10.8
通讯作者：
Kirabo A
中科院分区：
文献类型：
--
作者：
Ruggeri Barbaro N;Van Beusecum J;Xiao L;do Carmo L;Pitzer A;Loperena R;Foss JD;Elijovich F;Laffer CL;Montaniel KR;Galindo CL;Chen W;Ao M;Mernaugh RL;Alsouqi A;Ikizler TA;Fogo AB;Moreno H;Zhao S;Davies SS;Harrison DG;Kirabo A
先前的研究主要集中在肾脏和血管在盐诱导的血压调节中的作用；然而，最近的数据表明，钠在组织中积累，可以激活免疫细胞。我们试图在体内和体外检查盐引起人类单核细胞活化的机制。为了研究盐对人单核细胞的影响，从志愿者身上分离出单核细胞进行了几次体外实验。人单核细胞在体外暴露于升高的Na+会引起协调反应，包括异胶粘素(IsoLG)-加合物的形成，树突状细胞（DC）样形态的获得，活化标记物CD83和CD16的表达，以及促炎细胞因子肿瘤坏死因子-α，白细胞介素(IL)-6和IL-1β的产生增加。通过RNA测序检测，高盐还引起单核细胞基因表达的显著变化，并增强单核细胞向趋化因子CC基序趋化因子配体5的迁移。nadph氧化酶抑制减弱单核细胞活化和isolg加合物的形成。isolg加合物的增加与身体质量指数、脉压等危险因素相关。暴露于高盐环境的单核细胞刺激自体CD4+和CD8+ T细胞产生IL-17A。此外，为了评估盐在体内的作用，我们将从人身上分离的单核细胞和T细胞过继转移到免疫缺陷NSG小鼠身上。盐喂养人源化小鼠引起人T细胞的单核细胞依赖性激活，反映在骨髓中T细胞的增殖和积累。此外，我们对70名高血压前期受试者进行了横断面研究。采集血液进行流式细胞术分析，采用23Na磁共振成像进行组织钠测量。皮肤Na+含量高的人单核细胞表现出isolg加合物积累和CD83表达增加。在体外和体内钠暴露下，人类单核细胞在激活参数、向dc样表型的转化以及激活T细胞的能力方面均表现出协调的增加。单核细胞被钠激活的能力与体内心血管疾病的危险因素有关。因此，我们提出，除了肾脏和脉管系统外，免疫细胞如单核细胞也传递盐诱导的人类心血管风险。
Prior studies have focused on the role of the kidney and vasculature in salt-induced modulation of blood pressure; however, recent data indicate that sodium accumulates in tissues and can activate immune cells. We sought to examine mechanisms by which salt causes activation of human monocytes both in vivo and in vitro. To study the effect of salt in human monocytes, monocytes were isolated from volunteers to perform several in vitro experiments. Exposure of human monocytes to elevated Na+ex vivo caused a co-ordinated response involving isolevuglandin (IsoLG)-adduct formation, acquisition of a dendritic cell (DC)-like morphology, expression of activation markers CD83 and CD16, and increased production of pro-inflammatory cytokines tumour necrosis factor-α, interleukin (IL)-6, and IL-1β. High salt also caused a marked change in monocyte gene expression as detected by RNA sequencing and enhanced monocyte migration to the chemokine CC motif chemokine ligand 5. NADPH-oxidase inhibition attenuated monocyte activation and IsoLG-adduct formation. The increase in IsoLG-adducts correlated with risk factors including body mass index, pulse pressure. Monocytes exposed to high salt stimulated IL-17A production from autologous CD4+ and CD8+ T cells. In addition, to evaluate the effect of salt in vivo, monocytes and T cells isolated from humans were adoptively transferred to immunodeficient NSG mice. Salt feeding of humanized mice caused monocyte-dependent activation of human T cells reflected by proliferation and accumulation of T cells in the bone marrow. Moreover, we performed a cross-sectional study in 70 prehypertensive subjects. Blood was collected for flow cytometric analysis and 23Na magnetic resonance imaging was performed for tissue sodium measurements. Monocytes from humans with high skin Na+ exhibited increased IsoLG-adduct accumulation and CD83 expression. Human monocytes exhibit co-ordinated increases in parameters of activation, conversion to a DC-like phenotype and ability to activate T cells upon both in vitro and in vivo sodium exposure. The ability of monocytes to be activated by sodium is related to in vivo cardiovascular disease risk factors. We therefore propose that in addition to the kidney and vasculature, immune cells like monocytes convey salt-induced cardiovascular risk in humans.
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影响因子：
14.8
作者：
Davies, Sean S.;Amarnath, Venkataraman;Roberts, L. Jackson, II
通讯作者：
Roberts, L. Jackson, II
DOI：
10.1161/hypertensionaha.116.07289
发表时间：
2016-07
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Laffer CL;Scott RC 3rd;Titze JM;Luft FC;Elijovich F
通讯作者：
Elijovich F
影响因子：
16.8
作者：
Ingersoll MA;Platt AM;Potteaux S;Randolph GJ
通讯作者：
Randolph GJ
影响因子：
64.8
作者：
Kleinewietfeld, Markus;Manzel, Arndt;Titze, Jens;Kvakan, Heda;Yosef, Nir;Linker, Ralf A.;Muller, Dominik N.;Hafler, David A.
通讯作者：
Hafler, David A.
DOI：
10.1161/hypertensionaha.114.04975
发表时间：
2015-03
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Kamat NV;Thabet SR;Xiao L;Saleh MA;Kirabo A;Madhur MS;Delpire E;Harrison DG;McDonough AA
通讯作者：
McDonough AA