Harmon Ashlyn C, Ibrahim Tarek, Cornelius Denise C, Amaral Lorena M, Cunningham Mark W, Wallace Kedra, LaMarca Babbette
University of Mississippi Medical Center, Department of Pharmacology and Toxicology, Jackson, MS, United States.
University of Mississippi Medical Center, Department of Pharmacology and Toxicology, Jackson, MS, United States; Emergency Medicine, Jackson, MS, United States.
Pregnancy Hypertens. 2019 Jan;15:7-11. doi: 10.1016/j.preghy.2018.10.007. Epub 2018 Nov 2.
Preeclampsia (PE), new onset hypertension during pregnancy, is associated with a proinflammatory profile compared to normal pregnancy (NP). We hypothesize that CD4 T cells from PE patient placentas cause PE symptoms during pregnancy compared to those from NP women. CD4 T cells were isolated from placentas of PE and NP women using anti-CD4 magnetic separation, cultured in TexMACS medium at 37 °C in 5% CO, and injected intraperitoneally into nude-athymic rats on day 12 of gestation. On day 18, carotid catheters were implanted and on day 19, mean arterial pressure (MAP) was measured and blood and tissues were collected. MAP was 125 ± 2 mmHg in rats with NP CD4 T cells but increased to 140 ± 4 mmHg in rats with PE CD4 T cells. Significant differences in circulating cytokines tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17) and soluble fms-like tyrosine kinase-1 (sFlt-1) were found with PE vs NP CD4 T cells (TNF-α- PE = 167.4 pg/mL, NP = 79.4 pg/mL; IL-17-PE = 7.054 pg/mL, NP = 3.185 pg/mL; sFlt-1-PE = 90.7 pg/mL, NP = 58.2 pg/mL. In addition, renal cortical endothelin-1 (ET-1) mRNA expression increased 4.5 fold in rats with PE CD4 T cells versus those receiving to NP CD4 T cells. These data indicate an important role for placental PE CD4 T cells to cause many characteristics of PE during pregnancy.
子痫前期（PE）是孕期新发高血压，与正常妊娠（NP）相比具有促炎特征。我们假设，与NP女性胎盘来源的CD4 T细胞相比，PE患者胎盘来源的CD4 T细胞在孕期会引发PE症状。使用抗CD4磁珠分选法从PE和NP女性的胎盘中分离出CD4 T细胞，于37℃、5%二氧化碳条件下在TexMACS培养基中培养，并在妊娠第12天腹腔注射到无胸腺裸鼠体内。在第18天植入颈动脉导管，第19天测量平均动脉压（MAP）并采集血液和组织样本。接受NP CD4 T细胞的大鼠MAP为125±2 mmHg，而接受PE CD4 T细胞的大鼠MAP升高至140±4 mmHg。PE与NP CD4 T细胞相比，循环细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素-17（IL-17）和可溶性fms样酪氨酸激酶-1（sFlt-1）存在显著差异（TNF-α - PE = 167.4 pg/mL，NP = 79.4 pg/mL；IL-17 - PE = 7.054 pg/mL，NP = 3.185 pg/mL；sFlt-1 - PE = 90.7 pg/mL，NP = 58.2 pg/mL）。此外，与接受NP CD4 T细胞的大鼠相比，接受PE CD4 T细胞的大鼠肾皮质内皮素-1（ET-1）mRNA表达增加了4.5倍。这些数据表明，胎盘来源的PE CD4 T细胞在孕期引发PE的许多特征方面发挥着重要作用。
