来自angii型高血压供者的肾抗原呈递细胞转移血压并促进钠潴留。

Patricio Araos, Pablo León, Ignacio Gallegos-Pérez, Carolina Schäfer, Richard García-Betancourt, Edison Salas-Huenuleo, Carolina Prado, Víctor Barrientos, Jessica Liberona, Tomohiro Kojimahara, Stefanny M Figueroa, Cristián A Amador, Leandro J Carreño, Marcelo J Kogan, Alexis A Gonzalez, Rodrigo Pacheco, Rodrigo Alzamora, Heddwen L Brooks, Luis Michea
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引用次数: 0

摘要

抗原呈递细胞(APCs)存在于肾间质中,可能调节肾小管功能。我们假设血管紧张素II (Ang II)在肾apc中诱导高血压表型,有助于减少尿钠和高血压。我们评估了肾APCs在CD11c中作为BP调节剂的作用。注射白喉毒素(DT)的狗小鼠。DT消除70%的肾apc可防止血压升高、心脏肥厚、尿钠减少和NKCC2活化。其次,我们比较了肾和脾APCs过继转移对野生型小鼠血压和尿钠的影响。Angⅱ型小鼠肾APCs诱导短暂性血压升高和尿钠减少。相比之下,来自对照小鼠的肾apc或来自对照小鼠或注射angii的小鼠的脾apc没有改变血压或尿钠。在CD11c。从灌注血管的小鼠中过继性转移肾apc可使血压升高。然而,RAG1敲除小鼠,缺乏T细胞,在血管灌注小鼠肾apc过继转移后,血压没有增加。与对照肾apc相比,注入Ang ii的小鼠肾apc显示NOX2、SGK1和促炎细胞因子的表达增加。将肾APCs转移到正常血压的宿主后,细胞跟踪实验显示,APCs优先归巢到宿主肾脏,并且肾归巢趋化因子fractalkine (CX3CR1)的受体表达更高。我们得出结论,肾脏apc由于高水平的Ang II而获得高血压表型,从而具有调节肾脏钠处理的能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Renal antigen-presenting cells from ANG II hypertensive donors transfer blood pressure and promote sodium retention.

Antigen-presenting cells (APCs) are present in the renal interstitium and may modulate tubular function. We hypothesize that angiotensin II (Ang II) induces a prohypertensive phenotype in renal APCs, contributing to decreased natriuresis and hypertension. We evaluated the role of renal APCs as modulators of blood pressure (BP) in CD11c.DOG mice injected with diphtheria toxin (DT). Elimination of 70% of renal APCs by DT prevented the increase in BP, cardiac hypertrophy, decreased natriuresis, and sodium-potassium-chloride cotransporter type II (NKCC2) activation. Second, we compared the effect of the adoptive transfer of renal and splenic APCs on BP and natriuresis in wild-type mice. Renal APCs from Ang II mice induced a transient BP increase and reduced natriuresis. In contrast, renal APCs from control mice or splenic APCs from control or Ang II-infused mice did not modify BP or natriuresis. In CD11c.DOG mice depleted of dendritic cells (DCs), the adoptive transfer of renal APCs from Ang II-infused mice increased the BP. However, RAG1 knockout mice, devoid of T cells, did not present an increase in BP after the adoptive transfer of renal APCs of Ang II-infused mice. Renal APCs from Ang II-infused mice showed increased NOX2, SGK1, and pro-inflammatory cytokine expression compared with control renal APCs. Cell-tracking experiments of transferred renal APCs into a normotensive host showed preferential homing to the host kidneys and higher receptor expression for the renal-homing chemokine, fractalkine (CX3CR1). We conclude that renal APCs acquire a prohypertensive phenotype due to high Ang II levels, conferring the ability to modulate renal sodium handling.NEW & NOTEWORTHY Ablation of APCs prevented Ang II-induced hypertension, NKCC2 activation, and preserved natriuresis. Transfer of renal APCs from Ang II-mice increased BP and reduced natriuresis in recipient mice; renal APCs from normotensive mice or splenic APCs from Ang II-infused mice had no effect. The effect of renal APCs was dependent on the presence of T cells. Renal APCs from Ang II-mice showed preferential destination to the kidney and increased expression of cytokines.

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