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.
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Wheat germ agglutinin staining of the adult mouse heart transverse section. In their study, Diniz et al., shows microRNA-22 regulates dyslipidemia and energy expenditure. For more information please see pages 2885-2900. Image kindly provided by Da-Zhi Wang
Research Article|
November 23 2017
Natural killer cells mediate pathophysiology in response to reduced uterine perfusion pressure
Jamil Elfarra;
Jamil Elfarra
1Department of Obstetrics and Gynecology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, U.S.A.
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Lorena M. Amaral;
Lorena M. Amaral
2Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, U.S.A.
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Maggie McCalmon;
Maggie McCalmon
3Department of Emergency Medicine, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, U.S.A.
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Jeremy D. Scott;
Jeremy D. Scott
2Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, U.S.A.
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Mark W. Cunningham, Jr;
Mark W. Cunningham, Jr
2Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, U.S.A.
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Ashley Gnam;
Ashley Gnam
2Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, U.S.A.
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Tarek Ibrahim;
Tarek Ibrahim
2Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, U.S.A.
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Babbette LaMarca;
Babbette LaMarca
1Department of Obstetrics and Gynecology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, U.S.A.
2Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, U.S.A.
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Denise C. Cornelius
2Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, U.S.A.
3Department of Emergency Medicine, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, U.S.A.
Correspondence: Denise C. Cornelius ([email protected])
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Publisher: Portland Press Ltd
Received:
June 08 2017
Revision Received:
September 28 2017
Accepted:
October 13 2017
Accepted Manuscript online:
October 17 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (23): 2753–2762.
Article history
Received:
June 08 2017
Revision Received:
September 28 2017
Accepted:
October 13 2017
Accepted Manuscript online:
October 17 2017
Citation
Jamil Elfarra, Lorena M. Amaral, Maggie McCalmon, Jeremy D. Scott, Mark W. Cunningham, Ashley Gnam, Tarek Ibrahim, Babbette LaMarca, Denise C. Cornelius; Natural killer cells mediate pathophysiology in response to reduced uterine perfusion pressure. Clin Sci (Lond) 1 December 2017; 131 (23): 2753–2762. doi: https://doi.org/10.1042/CS20171118
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