Natural Killer Cells Mediate Pathophysiology in Response to Reduced Uterine Perfusion Pressure

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, 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 IFN- was 40.4±5.2 pg/mg in NP, to 72.17±3.2 pg/mg in RUPP, and 44.0±6.5 pg/mg in RUPP+anti-ASGM1 (p<0.05). Placental TNFα was 17.9&p...

Source: Clinical Science - October 17, 2017 Category: Biomedical Science Authors: Elfarra, J., Amaral, L. M., McCalmon, M., Scott, J. D., Cunningham, M. W., Gnam, A., Ibrahim, T., LaMarca, B., Cornelius, D. C. Tags: PublishAheadOfPrint Source Type: research