Functional NADPH oxidase 2 in T cells amplifies salt-sensitive hypertension and associated renal damage.

IF 3.7 2区 医学 Q1 PHYSIOLOGY American Journal of Physiology-renal Physiology Pub Date : 2023-08-01 Epub Date: 2023-06-15 DOI:10.1152/ajprenal.00014.2023
Samuel D Walton, John Henry Dasinger, Emily C Burns, Mary Cherian-Shaw, Justine M Abais-Battad, David L Mattson
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Abstract

Infiltrating T cells in the kidney amplify salt-sensitive (SS) hypertension and renal damage, but the mechanisms are not known. Genetic deletion of T cells (SSCD247-/-) or of the p67phox subunit of NADPH oxidase 2 (NOX2; SSp67phox-/-) attenuates SS hypertension in the Dahl SS rat. We hypothesized that reactive oxygen species produced by NOX2 in T cells drive the SS phenotype and renal damage. T cells were reconstituted by adoptively transferring splenocytes (∼10 million) from the Dahl SS (SS→CD247) rat, the SSp67phox-/- rat (p67phox→CD247), or only PBS (PBS→CD247) into the SSCD247-/- rat on postnatal day 5. Animals were instrumented with radiotelemeters and studied at 8 wk of age. There were no detectable differences in mean arterial pressure (MAP) or albuminuria between groups when rats were maintained on a low-salt (0.4% NaCl) diet. After 21 days of high-salt diet (4.0% NaCl), MAP and albuminuria were significantly greater in SS→CD247 rats compared with p67phox→CD247 and PBS→CD247 rats. Interestingly, there was no difference between p67phox→CD247 and PBS→CD247 rats in albuminuria or MAP after 21 days. The lack of CD3+ cells in PBS→CD247 rats and the presence of CD3+ cells in rats that received the T cell transfer demonstrated the effectiveness of the adoptive transfer. No differences in the number of CD3+, CD4+, or CD8+ cells were observed in the kidneys of SS→CD247 and p67phox→CD247 rats. These results indicate that reactive oxygen species produced by NOX2 in T cells participates in the amplification of SS hypertension and renal damage.NEW & NOTEWORTHY Our current work used the adoptive transfer of T cells that lack functional NADPH oxidase 2 into a genetically T cell-deficient Dahl salt-sensitive (SS) rat model. The results demonstrated that reactive oxygen species produced by NADPH oxidase 2 in T cells participate in the amplification of SS hypertension and associated renal damage and identifies a potential mechanism that exacerbates the salt-sensitive phenotype.

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T 细胞中的功能性 NADPH 氧化酶 2 会放大盐敏感性高血压和相关的肾损伤。
肾脏中浸润的T细胞会扩大盐敏感性(SS)高血压和肾损伤,但其机制尚不清楚。基因缺失 T 细胞(SSCD247-/-)或 NADPH 氧化酶 2(NOX2;SSp67phox-/-)的 p67phox 亚基可减轻 Dahl SS 大鼠的 SS 高血压。我们假设 T 细胞中的 NOX2 产生的活性氧驱动了 SS 表型和肾损伤。在大鼠出生后第 5 天,通过将来自 Dahl SS(SS→CD247)大鼠、SSp67phox-/-大鼠(p67phox→CD247)或仅 PBS(PBS→CD247)大鼠的脾细胞(1000 万个)收养转移到 SSCD247-/-大鼠体内,重建 T 细胞。在大鼠出生后第 5 天为其注射 SSCD247-/-大鼠(PBS→CD247)或仅注射 PBS(PBS→CD247)。当大鼠以低盐饮食(0.4% NaCl)维持生命时,各组之间的平均动脉压(MAP)或白蛋白尿没有可检测到的差异。高盐饮食(4.0% NaCl)21 天后,与 p67phox→CD247 和 PBS→CD247 大鼠相比,SS→CD247 大鼠的平均动脉压和白蛋白尿显著增加。有趣的是,21 天后,p67phox→CD247 和 PBS→CD247 大鼠的白蛋白尿或 MAP 没有差异。PBS→CD247 大鼠体内没有 CD3+ 细胞,而接受 T 细胞转移的大鼠体内有 CD3+ 细胞,这表明了采用转移的有效性。在 SS→CD247 和 p67phox→CD247 大鼠的肾脏中,没有观察到 CD3+、CD4+ 或 CD8+ 细胞数量的差异。这些结果表明,T 细胞中的 NOX2 产生的活性氧参与了 SS 高血压和肾脏损伤的扩大。结果表明,T 细胞中的 NADPH 氧化酶 2 产生的活性氧参与了 SS 高血压和相关肾损伤的扩大,并确定了盐敏感表型恶化的潜在机制。
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来源期刊
CiteScore
8.40
自引率
7.10%
发文量
154
审稿时长
2-4 weeks
期刊介绍: The American Journal of Physiology - Renal Physiology publishes original manuscripts on timely topics in both basic science and clinical research. Published articles address a broad range of subjects relating to the kidney and urinary tract, and may involve human or animal models, individual cell types, and isolated membrane systems. Also covered are the pathophysiological basis of renal disease processes, regulation of body fluids, and clinical research that provides mechanistic insights. Studies of renal function may be conducted using a wide range of approaches, such as biochemistry, immunology, genetics, mathematical modeling, molecular biology, as well as physiological and clinical methodologies.
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