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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    • "The most commonly accepted function ascribed to EVs is their role as shuttle vehicles for inter-cellular communication, involving paracrine or autocrine interactions or at a distance via the circulatory system to target cells (Raposo and Stoorvogel 2013). As pregnancy is considered to be a state of mild inflammation , it was speculated that placenta-derived EVs could provide a means of immunological communication between the mother and fetus in normal pregnancy, preventing early rejection (Redman and Sargent 2007). We (Messerli et al. 2010) and others (Germain et al. 2007) have shown that STBEVs can activate peripheral blood monocytes , inducing the release of various inflammatory cytokines, which has led to the suggestion that the higher levels of STBEVs may contribute to the systemic inflammatory response seen in PE (Redman et al. 2012). "
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    ABSTRACT: The literature on extracellular vesicles consists of rapidly expanding and often contradictory information. In this paper we attempt to review what is currently known regarding extracellular vesicles released specifically from human placental syncytiotrophoblast cells with a focus on the common but complex pregnancy-associated syndrome pre-eclampsia, where the level of syncytiotrophoblast extracellular vesicle release is significantly increased. We review common methods for syncytiotrophoblast extracellular vesicle derivation and isolation and we discuss the cargo of syncytiotrophoblast extracellular vesicles including proteins, RNA and lipids and their possible functions. A meta-analysis of available trophoblast-derived extracellular vesicle proteomic datasets revealed only three proteins in common: albumin, fibronectin-1 and plasminogen activator inhibitor-1, suggesting some variability in vesicle cargo, most likely reflecting stage and cell type of origin. We discuss the possible sources of variability that may have led to the low number of common markers, which has led us to speculate that markers and density in common use may not be strict criteria for identifying and isolating placenta-derived exosomes.
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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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    • "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.
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