Natural killer cells mediate pathophysiology in response to reduced uterine perfusion pressure.
Natural killer cells mediate pathophysiology in response to reduced uterine perfusion pressure.
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DOI：
10.1042/cs20171118
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发表时间：
2017-12-01
期刊：
影响因子：
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通讯作者：
Cornelius DC
中科院分区：
文献类型：
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作者：
Elfarra J;Amaral LM;McCalmon M;Scott JD;Cunningham MW Jr;Gnam A;Ibrahim T;LaMarca B;Cornelius DC
先兆子痫与高血压、小于胎龄儿和溶细胞性自然杀伤 (NK) 细胞增多有关。溶细胞性 NK 细胞在先兆子痫病理生理学中的具体作用尚未明确。我们假设降低子宫灌注压 (RUPP) 会刺激 NK 细胞的增殖和溶细胞活化，并且减少 RUPP 中的 NK 细胞可以预防高血压、宫内生长受限和胎盘缺血引起的炎症。 RUPP 在妊娠大鼠妊娠第 14 天（GD）诱导。 NK 细胞通过腹膜内注射耗尽。在 GD 15 和 17 上施用抗去唾液酸 GM1 抗体。通过流式细胞术对胎盘和循环 NK 细胞进行定量，在 GD 19 上测量平均动脉压 (MAP)、胎儿体重和细胞因子。胎盘 NK 细胞总数为正常妊娠 (NP; n=10) 中门控细胞的 7.4±2%，为 RUPP 中门控细胞的 16.5± 3% (n=10) 只大鼠。此外，RUPP 中溶细胞性胎盘 NK 细胞也增加。 RUPP（RUPP + 抗 ASGM1）中 NK 细胞的消耗显着改善了 MAP 和胎儿体重。 NP 中的 MAP 为 108± 2 mmHg，RUPP 中的 MAP 为 125± 2 mmHg，RUPP + 抗 ASGM1 中的 MAP 为 112± 2 mmHg (n=12)。胎儿体重在NP中为2.32±0.05，在RUPP中为1.8±0.04g，在RUPP+抗ASGM1中增加至2.0±0.04g。 NP中胎盘干扰素-γ（IFN-γ）为40.4±5.2 pg/mg，RUPP中为72.17±3.2 pg/mg，RUPP+抗ASGM1中为44.0±6.5 pg/mg（P<0.05）。胎盘肿瘤坏死因子-α（TNF-α）在NP中为17.9±1.7 pg/mg，在RUPP中为23.9±2.2 pg/mg，在RUPP +抗ASGM1中为12.9±2.3 pg/mg（P<0.05）。 NK 细胞的消耗显着降低了 RUPP 大鼠的 MAP、宫内生长受限和炎症，表明溶细胞 NK 细胞在先兆子痫病理生理学中很重要。
Preeclampsia is associated with hypertension, small-for-gestational-age babies, and increased cytolytic natural killer (NK) cells. The specific role of cytolytic NK cells in the pathophysiology of preeclampsia has not been clearly defined. We hypothesized that Reduced Uterine Perfusion Pressure (RUPP) stimulates proliferation and cytolytic activation of NK cells, and that reducing NK cells in RUPP would prevent hypertension, intrauterine growth restriction, and inflammation in response to placental ischemia. RUPP was induced on gestation day (GD) 14 in pregnant rats. NK cells were depleted by i.p. administration of anti-asialo GM1 antibody on GDs 15 and 17. Placental and circulating NK cells were quantified via flow cytometry, mean arterial pressure (MAP), fetal weights, and cytokines were measured on GD 19. Total placental NK cells were 7.4±2% of gated cells in normal pregnant (NP; n=10) and 16.5± 3% of gated cells in RUPP (n=10) rats. Furthermore, cytolytic placental NK cells also increased in RUPP. Depletion of NK cells in RUPP (RUPP + anti-ASGM1) significantly improved MAP and fetal weights. MAP was 108± 2 mmHg in NP, 125± 2 mmHg in RUPP, and 112± 2 mmHg in RUPP + anti-ASGM1 (n=12). Fetal weight was 2.32 ± 0.05 in NP, 1.8± 0.04g in RUPP, and increased to 2.0± 0.04g in RUPP + anti-ASGM1. Placental interferon-γ (IFN-γ) was 40.4± 5.2 pg/mg in NP, 72.17± 3.2 pg/mg in RUPP, and 44.0± 6.5 pg/mg in RUPP + anti-ASGM1 (P<0.05). Placental tumor necrosis factor-α (TNF-α) was 17.9± 1.7 pg/mg in NP, 23.9± 2.2 pg/mg in RUPP, and 12.9± 2.3 pg/mg in RUPP + anti-ASGM1 (P<0.05). Depletion of NK cells significantly lowered MAP, intrauterine growth restriction, and inflammation in RUPP rats indicating that cytolytic NK cells are important in preeclampsia pathophysiology.
外周血CD8αα+CD11C+MHC-II+CD3-细胞减弱大鼠的自身免疫性肾小球肾炎。
影响因子：
19.6
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通讯作者：
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