Functional NADPH oxidase 2 in T cells amplifies salt-sensitive hypertension and associated renal damage.
Functional NADPH oxidase 2 in T cells amplifies salt-sensitive hypertension and associated renal damage.
复制标题
T 细胞中的功能性 NADPH 氧化酶 2 会加剧盐敏感性高血压和相关的肾损伤。
DOI：
10.1152/ajprenal.00014.2023
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Mattson,DavidL
中科院分区：
文献类型：
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作者：
Walton,SamuelD;Dasinger,JohnHenry;Burns,EmilyC;Cherian-Shaw,Mary;Abais-Battad,JustineM;Mattson,DavidL
肾脏中的浸润性T细胞会放大盐敏感性（SS）高血压和肾损伤，但其机制尚不清楚。在Dahl SS大鼠中，T细胞（SSCD 247 −/−）或NADPH氧化酶2（NOX 2; SSp 67 phox −/−）的p67 phox亚基的基因缺失可减轻SS高血压。我们假设T细胞中NOX 2产生的活性氧簇驱动SS表型和肾损伤。在出生后第5天，通过将来自Dahl SS（SS→ CD 247）大鼠、SSp 67 phox −/−大鼠（p67 phox → CD 247）或仅PBS（PBS→ CD 247）的脾细胞（1000万）过继转移到SSCD 247 −/−大鼠中来重建T细胞。在8周龄时，用无线电遥测仪对动物进行仪器测量和研究。当大鼠维持低盐（0.4%NaCl）饮食时，各组之间的平均动脉压（MAP）或蛋白尿没有可检测到的差异。在高盐饮食（4.0%NaCl）21天后，SS→ CD 247大鼠的MAP和蛋白尿显著高于p67 phox → CD 247和PBS→ CD 247大鼠。有趣的是，21天后，p67 phox → CD 247和PBS→ CD 247大鼠之间的蛋白尿或MAP没有差异。PBS→ CD 247大鼠中缺乏CD 3+细胞，而接受T细胞转移的大鼠中存在CD 3+细胞，证明了过继转移的有效性。在SS→ CD 247和p67 phox → CD 247大鼠的肾脏中未观察到CD 3+、CD 4+或CD 8+细胞数量的差异。这些结果表明，活性氧在T细胞中产生的NOX 2参与放大SS高血压和肾damage.NEW & NOTEWORTHY我们目前的工作采用过继转移的T细胞，缺乏功能性NADPH氧化酶2到一个遗传性T细胞缺陷型达尔盐敏感（SS）大鼠模型。结果表明，T细胞中NADPH氧化酶2产生的活性氧参与SS高血压和相关肾损伤的放大，并确定了一种加剧盐敏感表型的潜在机制。
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 p67phoxsubunit 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 onpostnatal 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 & NOTEWORTHYOur 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.