Salt-sensitive increase in macrophages in the kidneys of Dahl SS rats
Salt-sensitive increase in macrophages in the kidneys of Dahl SS rats
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DOI：
10.1152/ajprenal.00096.2019
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发表时间：
2019-08-01
影响因子：
4.2
通讯作者：
Mattson, David L.
中科院分区：
文献类型：
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作者：
Fehrenbach, Daniel J.;Abais-Battad, Justine M.;Mattson, David L.
对Dahl盐敏感（SS）大鼠的研究表明，肾脏CD 3（+）T细胞和艾德-1 +巨噬细胞参与盐敏感性高血压和肾损伤的发生。本研究表明，在高盐饮食喂养的Dahl SS大鼠中伴随肾脏肥大和蛋白尿的肾脏免疫细胞的增加在受保护免于SS疾病表型的Sprague-Dawley和SSBN 13大鼠中不存在。流式细胞术分析表明，SS肾中>70%的免疫细胞是M1巨噬细胞。肾骨髓细胞的PCR分析显示盐诱导的与Toll样受体信号传导相关的84个基因中的9个上调，其中Toll样受体4/CD 14/MD 2复合物显著上调。因为SS肾脏中巨噬细胞显著增加。我们使用脂质体包封的氯膦酸盐（Clod）来消耗巨噬细胞并评估它们对盐敏感性高血压和肾损伤的贡献。Dahl SS动物给予含Clod的脂质体（Clod-Lipo）。Clod或含PBS的脂质体作为媒介物对照。Clod-Lipo处理使循环和脾脏巨噬细胞消耗了约50%;然而，与我们的假设相反，Clod-Lipo处理的动物在血压和白蛋白尿方面出现了加重的盐敏感性反应，并伴有肾T和B细胞增加。有趣的是，那些用Clod治疗的动物也表现出恶化的表型，但它比Clod-Lipo治疗的动物不那么严重，并且与肾免疫细胞数量的变化无关。在这里，我们已经表明，Dahl SS动物的肾巨噬细胞维持M1促炎表型，以响应增加的饮食盐，并强调了Clod-Lipo巨噬细胞耗竭的潜在不良影响。
Studies of Dahl salt-sensitive (SS) rats have shown that renal CD3(+) T cells and ED-1 + macrophages are involved in the development of salt-sensitive hypertension and renal damage. The present study demonstrated that the increase in renal immune cells, which accompanies renal hypertrophy and albuminuria in high-salt diet-fed Dahl SS rats, is absent in Sprague-Dawley and SSBN13 rats that are protected from the SS disease phenotype. Flow cytometric analysis demonstrated that >70% of the immune cells in the SS kidney are M1 macrophages. PCR profiling of renal myeloid cells showed a salt-induced upregulation in 9 of 84 genes related to Toll-like receptor signaling, with notable upregulation of the Toll-like receptor 4/CD14/MD2 complex. Because of the prominent increase in macrophages in the SS kidney. we used liposome-encapsulated clodronate (Clod) to deplete macrophages and assess their contribution to salt-sensitive hypertension and renal damage. Dahl SS animals were administered either Clod-containing liposomes (Clod-Lipo). Clod, or PBS-containing liposomes as a vehicle control. Clod-Lipo treatment depleted circulating and splenic macrophages by similar to 50%; however, contrary to our hypothesis, Clod-Lipo-treated animals developed an exacerbated salt-sensitive response with respect to blood pressure and albuminuria, which was accompanied by increased renal T and B cells. Interestingly, those treated with Clod also demonstrated an exacerbated phenotype, but it was less severe than Clod-Lipo-treated animals and independent of changes to the number of renal immune cells. Here, we have shown that renal macrophages in Dahl SS animals sustain a M1 proinflam-matory phenotype in response to increased dietary salt and highlighted potential adverse effects of Clod-Lipo macrophage depletion.