Owen T Herrock, Evangeline Deer, Lorena M Amaral, Nathan Campbell, James Lemon, Nicole Ingram, Denise C Cornelius, Ty W Turner, Sarah Fitzgerald, Tarek Ibrahim, Ralf Dechend, Gerd Wallukat, Babbette LaMarca
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We hypothesize that B2 cells cause hypertension, natural killer (NK) cell activation, and complement activation during pregnancy through the production of AT1-AA. To test this hypothesis, total splenic B cells and B2 cells were isolated from normal pregnant (NP) or RUPP rats on gestational day (GD)19 and adoptively transferred into GD12 NP rats. A group of recipient rats was treated with a specific inhibitor peptide of AT1-AA. On GD19, mean arterial pressure was measured, tissues were collected, activated NK cells were measured by flow cytometry, and AT1-AA was measured by cardiomyocyte assay. NP recipients of RUPP B cells or RUPP B2 cells had increased mean arterial pressure, AT1-AA, and circulating activated NK cells compared with recipients of NP B cells. Hypertension in NP recipients of RUPP B cells or RUPP B2 was attenuated with AT1-AA blockade. This study demonstrates that B cells and B2 cells from RUPP rats cause hypertension and increased AT1-AA and NK cell activation in response to placental ischemia during pregnancy.<b>NEW & NOTEWORTHY</b> This study demonstrates that placental ischemia-stimulated B2 cells induce hypertension and circulating natural killer cell activation and angiotensin II type 1 receptor production in normal pregnant rats.</p>","PeriodicalId":7588,"journal":{"name":"American Journal of Physiology-renal Physiology","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844978/pdf/","citationCount":"0","resultStr":"{\"title\":\"B2 cells contribute to hypertension and natural killer cell activation possibly via AT1-AA in response to placental ischemia.\",\"authors\":\"Owen T Herrock, Evangeline Deer, Lorena M Amaral, Nathan Campbell, James Lemon, Nicole Ingram, Denise C Cornelius, Ty W Turner, Sarah Fitzgerald, Tarek Ibrahim, Ralf Dechend, Gerd Wallukat, Babbette LaMarca\",\"doi\":\"10.1152/ajprenal.00190.2022\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Preeclampsia, new onset hypertension during pregnancy, is associated with activated T helper cells (Th) and B cells secreting agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA). 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引用次数: 0
摘要
子痫前期(妊娠期新发高血压)与活化的 T 辅助细胞(Th)和 B 细胞分泌针对血管紧张素 II 1 型受体(AT1-AA)的激动性自身抗体有关。胎盘缺血的子宫灌注压降低(RUPP)模型再现了这些特征。我们的研究表明,Th-B 细胞通讯是导致 AT1-AA 和 RUPP 大鼠子痫前期症状的原因。B2 细胞是经典的 B 细胞,它们与 Th 细胞交流,然后转化为记忆 B 细胞。我们假设 B2 细胞通过产生 AT1-AA 导致妊娠期高血压、自然杀伤(NK)细胞活化和补体活化。为了验证这一假设,我们在妊娠日(GD)19从正常妊娠(NP)大鼠或RUPP大鼠体内分离出脾脏B细胞和B2细胞,并将其移植到GD12 NP大鼠体内。一组受体大鼠接受AT1-AA特异性抑制肽治疗。在 GD19 日测量平均动脉压,收集组织,用流式细胞术测量活化的 NK 细胞,用心肌细胞检测法测量 AT1-AA。与 NP B 细胞受体相比,RUPP B 细胞或 RUPP B2 细胞的 NP 受体的平均动脉压、AT1-AA 和循环活化的 NK 细胞均有所增加。接受 RUPP B 细胞或 RUPP B2 细胞的 NP 患者的高血压在 AT1-AA 阻断后有所缓解。这项研究表明,RUPP大鼠的B细胞和B2细胞会导致妊娠期高血压、AT1-AA和NK细胞活化增加,从而对胎盘缺血产生反应。
B2 cells contribute to hypertension and natural killer cell activation possibly via AT1-AA in response to placental ischemia.
Preeclampsia, new onset hypertension during pregnancy, is associated with activated T helper cells (Th) and B cells secreting agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA). The reduced uterine perfusion pressure (RUPP) model of placental ischemia recapitulates these characteristics. We have shown that Th-B cell communication contributes to AT1-AA and symptoms of preeclampsia in the RUPP rat. B2 cells are classical B cells that communicate with Th cells and are then transformed into memory B cells. We hypothesize that B2 cells cause hypertension, natural killer (NK) cell activation, and complement activation during pregnancy through the production of AT1-AA. To test this hypothesis, total splenic B cells and B2 cells were isolated from normal pregnant (NP) or RUPP rats on gestational day (GD)19 and adoptively transferred into GD12 NP rats. A group of recipient rats was treated with a specific inhibitor peptide of AT1-AA. On GD19, mean arterial pressure was measured, tissues were collected, activated NK cells were measured by flow cytometry, and AT1-AA was measured by cardiomyocyte assay. NP recipients of RUPP B cells or RUPP B2 cells had increased mean arterial pressure, AT1-AA, and circulating activated NK cells compared with recipients of NP B cells. Hypertension in NP recipients of RUPP B cells or RUPP B2 was attenuated with AT1-AA blockade. This study demonstrates that B cells and B2 cells from RUPP rats cause hypertension and increased AT1-AA and NK cell activation in response to placental ischemia during pregnancy.NEW & NOTEWORTHY This study demonstrates that placental ischemia-stimulated B2 cells induce hypertension and circulating natural killer cell activation and angiotensin II type 1 receptor production in normal pregnant rats.
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.