Microparticles and immunomodulation in pregnancy and pre-eclampsia

University of Oxford, Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Journal of Reproductive Immunology (Impact Factor: 2.82). 12/2007; 76(1-2):61-7. DOI: 10.1016/j.jri.2007.03.008
Source: PubMed


Cellular microparticles are ubiquitously shed from cell membranes or secreted as endocytic vesicles called exosomes. Shed microparticles are >/=100nm in size and are generated during apoptosis or necrosis. In contrast, exosomes are smaller (<100nm), express more limited protein content and are released from late endosomes. Both membrane particles and exosomes can be detected in the circulation in non-pregnant and pregnant women. In the former, they are increased in conditions associated with systemic inflammation such as sepsis or metabolic syndrome. During pregnancy, they are also associated with pre-eclampsia and include not only particles derived from platelets, endothelium and various leukocytes but also syncytiotrophoblast-derived microparticles. Syncytiotrophoblast membrane microparticles (often called STBMs) interact with both immune and endothelial cells. They may contribute to the systemic inflammatory response of both normal and pre-eclamptic pregnancies, although inhibitory activity has also been described. Moreover, trophoblast-derived exosomes may contribute to or cause the downregulation of T cell activity that has been repeatedly observed during pregnancy. Deletion of activate T cells which express Fas ligand by Fas-expressing exosomes derived from trophoblast may contribute to immunoregulation necessary for normal pregnancy.

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    • "Epidemiological evidence supporting this idea has been published by many groups, suggesting the importance of the maternal immune system in the pathogenesis of placental originated diseases. Different studies have been performed to characterize the local and systemic immune milieu of these patients as an explanation for the abnormalities of placentation observed in PE (55–57). Normal pregnancy is considered as a (T helper) Th2 type immunological state that favors an immunosuppressive environment in order to prevent fetal rejection (58). "
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    ABSTRACT: Menstrual-derived stem cells (MenSCs) are a new source of mesenchymal stem cells isolated from the menstrual fluid. Currently, there is a growing interest in their clinical potential due to fact that they are multipotent, highly proliferative, and easy to obtain in a non-invasive manner. Sampling can be repeated periodically in a simplified and reproducible manner devoid of complications that no existing cell source can match. MenSCs are also free of ethical dilemmas, and display novel properties with regard to presently known adult derived stem cells. This review details their distinctive biological properties regarding immunophenotype and function, proliferation rate, differentiation potential, and paracrine effects mediated by secreted factors. Their possible role in antenatal diagnosis is also discussed. While more insight on their immunomodulatory and diagnostic properties is needed, the impact of clinical and epidemiological factors, such as age, use of contraceptives, or hormonal status still requires further investigations to properly assess their current and future use in clinical application and diagnosis.
    Frontiers in Immunology 05/2014; 5:205. DOI:10.3389/fimmu.2014.00205
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    • "MPs have been documented to participate in processes of coagulation, inflammation, vascular reactivity, angiogenesis, metastasis, and the balance between cell proliferation, differentiation, cell survival and apoptosis [2]–[4]. This is possible because they carry cellular components from their cells of origin, including bioactive lipids, membrane-bound proteins, cytosolic proteins, viral contaminants, mRNA, and even organelles and DNA fragments [3]–[5]. These components can be transported to other cells via membrane fusion, or engulfment of MPs with the target cell membrane [6]. "
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    ABSTRACT: Microparticles (MPs) are sub-micron membrane vesicles (100-1000 nm) shed from normal and pathologic cells due to stimulation or apoptosis. MPs can be found in the peripheral blood circulation of healthy individuals, whereas elevated concentrations are found in pregnancy and in a variety of diseases. Also, MPs participate in physiological processes, e.g., coagulation, inflammation, and angiogenesis. Since their clinical properties are important, we have developed a new methodology based on nano-imaging that provides significant new data on MPs nanostructure, their composition and function. We are among the first to characterize by direct-imaging cryogenic transmitting electron microscopy (cryo-TEM) the near-to-native nanostructure of MP systems isolated from different cell types and stimulation procedures. We found that there are no major differences between the MP systems we have studied, as most particles were spherical, with diameters from 200 to 400 nm. However, each MP population is very heterogeneous, showing diverse morphologies. We investigated by cryo-TEM the effects of standard techniques used to isolate and store MPs, and found that either high-g centrifugation of MPs for isolation purposes, or slow freezing to -80°C for storage introduce morphological artifacts, which can influence MP nanostructure, and thus affect the efficiency of these particles as future diagnostic tools.
    PLoS ONE 12/2013; 8(12):e83680. DOI:10.1371/journal.pone.0083680 · 3.23 Impact Factor
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    • "In particular, inappropriate activation of the immune system may be associated with the development of this syndrome. Preeclampsia is characterized as a state of the excessive maternal inflammatory response with a predominance of the production of Th1 cytokines, such as IL-2, IL-6, IL-8, IFN-␥, TNF-␣, as well as IL-12 (Saito et al., 1999; Darmochwal-Kolarz et al., 2002; Saito and Sakai, 2003; Sakai et al., 2004; Tosun et al., 2010; Redman and Sargent, 2007). "
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    ABSTRACT: The aim of this study was to estimate the prevalence of CD3(+)CD4(+) T lymphocytes producing IL-17, IL-2, IFN-γ, and IL-4, plus CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells, in peripheral blood of patients with preeclampsia and healthy women in the third trimester of normal pregnancy. Another purpose was to assess the immunosuppressive activity of Treg cells from patients with preeclampsia compared with controls. Thirty-four preeclampsia patients and 27 healthy pregnant women were included. The percentages of CD4(+)CD25(+)FoxP3(+) Treg cells and CD3(+)CD4(+) T lymphocytes with intracellular expressions of cytokines were estimated using monoclonal antibodies and flow cytometry. In vitro functional assays were performed using a Treg Cell Isolation Kit and (3)H-thymidine incorporation assays. The percentage of CD3(+)CD4(+) T lymphocytes producing IL-17A was significantly higher in preeclampsia than in healthy, normotensive pregnant women in the third trimester (p<0.001). The population of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower in the study group compared with controls (p<0.05). There was no change in the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes from preeclampsia patients without Treg cells and after addition of autologous Treg cells. In normal pregnancy, the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes was significantly higher without Treg cells compared with the response after addition of autologous Treg cells (p<0.05). The results suggest up-regulation of the Th17 immune response in preeclampsia. The decreased number and function of Treg cells may be responsible for activating the inflammatory response characteristic of this disorder. In preeclampsia, the predominance of Th17 immunity could act through modulating the Th1/Th2 immune balance.
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