Splenocyte transfer exacerbates salt-sensitive hypertension in rats.

Splenocyte transfer exacerbates salt-sensitive hypertension in rats.
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DOI:
10.1113/ep088340
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发表时间:
2020-05
影响因子:
2.7
通讯作者:
Mattson DL
Mattson DL
中科院分区:
医学4区
文献类型:
--
作者:
Fehrenbach DJ;Dasinger JH;Lund H;Zemaj J;Mattson DL

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越来越多的证据表明,在高血压和肾损伤的进展过程中,免疫系统激活导致需要新的方法来研究单个细胞类型。免疫细胞的转移是一种强大的工具,可以隔离特定亚群的影响。Rag 1 −/−小鼠的转移研究已经证明了T细胞活化在高血压中的重要作用,但这种方法在大鼠模型中取得的成功有限。使用T细胞缺陷型达尔盐敏感(SS)大鼠SSCD 247 −/−,我们假设从SS野生型动物转移到SSCD 247 −/−动物的脾细胞将填充T细胞区室。Dahl SS背景为研究盐敏感性高血压提供了一个模型;因此,我们还测试了供体的饮食盐含量是否会赋予受体不同的盐敏感性。为了测试这一点,捐助者保持在低盐或高盐饮食,并在出生后第5天的收件人接受脾细胞转移从这些组之一之前,高盐饮食的挑战。我们发现,当大鼠被喂食低盐时,脾细胞转移会升高血压,而当大鼠被喂食高盐时,脾细胞转移会加剧血压的盐敏感性升高。此外,脾细胞的转移加重了肾损伤。最后,我们证实了T细胞在循环和脾脏中的存在,并且在接受转移的那些中,免疫细胞(包括T细胞、巨噬细胞和B细胞)向肾脏中的浸润增加。有趣的是,来自低盐或高盐饮食的供体的脾细胞的来源并没有显著影响这些盐敏感表型。
Increasing evidence of immune system activation during the progression of hypertension and renal injury has led to a need for new methods to study individual cell types. Transfer of immune cells serves as a powerful tool to isolate effects of specific subsets. Transfer studies in Rag1−/− mice have demonstrated an important role of T-cell activation in hypertension, but this approach has yielded limited success in rat models. Using the T-cell-deficient Dahl salt-sensitive (SS) rat, SSCD247−/−, we hypothesized that splenocyte transfer from SS wild-type animals into SSCD247−/− animals would populate the T-cell compartment. The Dahl SS background provides a model for studying salt-sensitive hypertension; therefore, we also tested whether the dietary salt content of the donor would confer differential salt sensitivity in the recipient. To test this, donors were maintained on either a low-salt or a high-salt diet, and at postnatal day 5 the recipients received splenocyte transfer from one of these groups before a high-salt diet challenge. We showed that splenocyte transfer elevated blood pressures while rats were fed low salt and exacerbated the salt-sensitive increase in pressure when they were fed fed high salt. Furthermore, transfer of splenocytes conferred exacerbated renal damage. Lastly, we confirmed the presence of T cells in the circulation and in the spleen, and that infiltration of immune cells, including T cells, macrophages and B cells, into the kidney was elevated in those receiving the transfer. Interestingly, the source of the splenocytes, from donors fed either a low-salt or a high-salt diet, did not significantly affect these salt-sensitive phenotypes.
DOI: 10.1084/jem.180.6.2239
发表时间: 1994-12-01
期刊: The Journal of experimental medicine
影响因子: --
作者:
Weiss RA;Madaio MP;Tomaszewski JE;Kelly CJ
通讯作者: Kelly CJ