Expression of dNK cells and their cytokines in twin pregnancies with preeclampsia

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Abstract

OBJECTIVES:

To assess the expression of decidual natural killer (dNK) cells and their cytokines in twin pregnancies with preeclampsia.

METHODS:

This was a prospective case-control study. The inclusion criteria were diamniotic (monochorionic or dichorionic) twin pregnancies in the third trimester with negative serological results for infectious diseases; absence of major fetal abnormalities or twin-twin transfusion syndrome; and no history of administration of corticosteroids in this pregnancy. The control group (CG) included uncomplicated twin pregnancies, and the preeclampsia group (PEG) included twin gestations with clinical and laboratory confirmation of the disease according to well-established criteria. Samples of the decidua were obtained and analyzed by immunohistochemistry for the expression of dNK cells and interleukins (ILs) 10, 12 and 15. In addition, maternal serum samples were collected to determine the levels of these interleukins.

RESULTS:

Thirty twin pregnancies were selected: 20 in the control group (CG) and 10 in the preeclampsia group (PEG). The PEG showed strong placental immunostaining for IL-15 ( p=0.001) and high maternal serum levels of IL-10 (22.7 vs. 11.9 pg/mL, p=0.024) and IL-15 (15.9 vs. 7.4 pg/mL, p=0.024).

CONCLUSION:

A higher maternal serum concentration of both pro- and anti-inflammatory factors was observed in the twin pregnancies in the PEG. However, no difference in placental expression of IL-10 was found between the groups. These findings may suggest that maternal attempts to balance these interleukins were not sufficient to cause a placental response, and this failure may contribute to the development of preeclampsia.

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Most cited references 26

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Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes

SC Clark, L Fitz, RM Hewick … (1989)

We have identified and purified a novel cytokine, NK cell stimulatory factor (NKSF), from the cell-free supernatant fluid of the phorbol diester-induced EBV-transformed human B lymphoblastoid cell line RPMI 8866. NKSF activity is mostly associated to a 70-kD anionic glycoprotein. The purified 70-kD protein, isolated from an SDS-PAGE gel, yields upon reduction two small species of molecular masses of 40 and 35 kD, suggesting that this cytokine is a heterodimer. When added to human PBL, purified NKSF preparations induce IFN-gamma production and synergize with rIL-2 in this activity, augment the NK cell-mediated cytotoxicity of PBL preparations against both NK-sensitive and NK- resistant target cell lines, and enhance the mitogenic response of T cells to mitogenic lectins and phorbol diesters. The three activities remain associated through different purification steps resulting in a 9,200-fold purification, and purified NKSF mediates the three biological activities at concentrations in the range of 0.1-10 pM. These data strongly suggest that the same molecule mediates these three activities, although the presence of traces of contaminant peptides even in the most purified NKSF preparations does not allow us to exclude the possibility that distinct biologically active molecules have been co-purified. The absence of other known cytokines in the purified NKSF preparations, the unusual molecular conformation of NKSF, the high specific activity of the purified protein, and the spectrum of biological activities distinguish NKSF from other previously described cytokines.

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Uterine NK cells and macrophages in pregnancy.

Marijke Faas, Paul de Vos (2017)

The presence of immune cells in the placental bed is important for both mother and child. Although various immune cells can be found in the placental bed, such as regulatory T cells and dendritic cells, uterine NK cells and macrophages are the most prominent immune cells in the placental bed in early pregnancy. uNK cell and macrophage numbers in the placental bed decrease in the third trimester. These cells seem to be specifically adapted for their function and environment. uNK cells do not show cytotoxic activity, but are producers of cytokines, growth factors and many other factors. uNK cell function is regulated by inhibitory and activating receptors binding to HLA class I on trophoblast cells. uNK cells are also involved in regulating trophoblast invasion. Macrophages mainly show an M2-like phenotype and also produce cytokines and various other factors. They are important in phagocytosis of various cells and cell debris in the placental bed. Both cell types are also involved in angiogenesis and spiral artery remodeling in the placental bed. In this review we will elaborate on the most important functions of uNK cells and macrophages in the placental bed in humans. We will also discuss animal models, since they may provide clues for function of uNK cells and macrophages in humans.

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Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction.

Jeffrey S. Gilbert, Lisa B LaMarca, Patrick B. Murphy … (2008)

Studies over the last decade have provided exciting new insights into potential mechanisms underlying the pathogenesis of preeclampsia. The initiating event in preeclampsia is generally regarded to be placental ischemia/hypoxia, which in turn results in the elaboration of a variety of factors from the placenta that generates profound effects on the cardiovascular system. This host of molecules includes factors such as soluble fms-like tyrosine kinase-1, the angiotensin II type 1 receptor autoantibody, and cytokines such as tumor necrosis factor-alpha, which generate widespread dysfunction of the maternal vascular endothelium. This dysfunction manifests as enhanced formation of factors such as endothelin, reactive oxygen species, and augmented vascular sensitivity to angiotensin II. Alternatively, the preeclampsia syndrome may also be evidenced as decreased formation of vasodilators such as nitric oxide and prostacyclin. Taken together, these alterations cause hypertension by impairing renal pressure natriuresis and increasing total peripheral resistance. Moreover, the quantitative importance of the various endothelial and humoral factors that mediate vasoconstriction and elevation of arterial pressure during preeclampsia remains to be elucidated. Thus identifying the connection between placental ischemia/hypoxia and maternal cardiovascular abnormalities in hopes of revealing potential therapeutic regimens remains an important area of investigation and will be the focus of this review.

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Author and article information

Journal

Journal ID (nlm-ta): Clinics (Sao Paulo)

Journal ID (iso-abbrev): Clinics (Sao Paulo)

Journal ID (publisher-id): clin

Title: Clinics

Publisher: Faculdade de Medicina / USP

ISSN (Print): 1807-5932

ISSN (Electronic): 1980-5322

Publication date (Electronic): 30 October 2019

Publication date (Print): 2019

Volume: 74

Electronic Location Identifier: e1200

Affiliations

[I ]Departamento de Ginecologia e Obstetricia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.

[II ]Departamento de Patologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR.

Author notes

*Corresponding author. E-mail: mlbrizot@ 123456uol.com.br

Author information

Isabela K.R. Agra https://orcid.org/0000-0003-4980-0378

Adolfo W. Liao https://orcid.org/0000-0001-6295-5089

Mara S. Hoshida https://orcid.org/0000-0003-2232-4631

Regina Schultz https://orcid.org/0000-0002-8736-8208

Marcello P. Toscano https://orcid.org/0000-0002-6316-3566

Rossana P.V. Francisco https://orcid.org/0000-0002-9981-8069

Marcelo Zugaib https://orcid.org/0000-0003-1155-2671

Maria L. Brizot https://orcid.org/0000-0002-6135-4844

Article

Publisher ID: cln_74p1

DOI: 10.6061/clinics/2019/e1200

PMC ID: 6820511

PubMed ID: 31721933

SO-VID: ba829182-5171-4cf0-b8bb-ee224f632c8f

License:

This is an Open Access article distributed under the terms of the Creative Commons License ( http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.

Expression of dNK cells and their cytokines in twin pregnancies with preeclampsia

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Abstract

OBJECTIVES:

METHODS:

RESULTS:

CONCLUSION:

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Most cited references 26

Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes

Uterine NK cells and macrophages in pregnancy.

Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction.

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