T cell exosomes induce cholesterol accumulation in human monocytes via phosphatidylserine receptor. J Cell Physiol

Department of Physiology and Membrane Biology, University of California Davis, Davis, California 95616, USA.
Journal of Cellular Physiology (Impact Factor: 3.84). 07/2007; 212(1):174-81. DOI: 10.1002/jcp.21013
Source: PubMed


Activated T lymphocytes release vesicles, termed exosomes, enriched in cholesterol and exposing phosphatidylserine (PS) at their outer membrane leaflet. Although CD4(+) activated T lymphocytes infiltrate an atherosclerotic plaque, the effects of T cell exosomes on the atheroma-associated cells are not known. We report here that exosomes isolated from the supernatants of activated human CD4(+) T cells enhance cholesterol accumulation in cultured human monocytes and THP-1 cells. Lipid droplets found in the cytosol of exosome-treated monocytes contained both cholesterol ester and free cholesterol. Anti-phosphatidylserine receptor antibodies recognized surface protein on the monocyte plasma membrane and prevented exosome-induced cholesterol accumulation, indicating that exosome internalization is mediated via endogenous phosphatidylserine receptor. The production of proinflammatory cytokine TNF-alpha enhanced in parallel with monocyte cholesterol accumulation. Our data strongly indicate that exosomes released by activated T cells may represent a powerful, previously unknown, atherogenic factor.

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Available from: Maria Svetlova, Mar 30, 2015
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    • "This suggests a relationship between exosome lipid composition and their functionality. Because of their high cholesterol content and their accumulation in recipient endosomes, exosomes can be implicated in cholesterol-related storage disease and they can modify the lipid homeostasis of target cells [5] [55] [56]. 3.1. "
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    ABSTRACT: Exosomes are nanovesicles that have emerged as a new intercellular communication system between an intracellular compartment of a donor cell towards the periphery or an internal compartment of a recipient cell. The bioactivity of exosomes resides not only in their protein and RNA contents but also in their lipidic molecules. Exosomes display original lipids organized in a bilayer membrane and along with the lipid carriers such as fatty acid binding proteins that they contain, exosomes transport bioactive lipids. Exosomes can vectorize lipids such as eicosanoids, fatty acids, and cholesterol, and their lipid composition can be modified by in-vitro manipulation. They also contain lipid related enzymes so that they can constitute an autonomous unit of production of various bioactive lipids. Exosomes can circulate between proximal or distal cells and their fate can be regulated in part by lipidic molecules. Compared to their parental cells, exosomes are enriched in cholesterol and sphingomyelin and their accumulation in cells might modulate recipient cell homeostasis. Exosome release from cells appears to be a general biological process. They have been reported in all biological fluids from which they can be recovered and can be monitors of specific pathophysiological situations. Thus, the lipid content of circulating exosomes could be useful biomarkers of lipid related diseases. Since the first lipid analysis of exosomes ten years ago detailed knowledge of exosomal lipids has accumulated. The role of lipids in exosome fate and bioactivity and how they constitute an additional lipid transport system are considered in this review.
    Biochimica et Biophysica Acta 10/2013; 1841(1). DOI:10.1016/j.bbalip.2013.10.004 · 4.66 Impact Factor
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    • "Since exosomes are enriched in cholesterol and can transfer material between cells, it has been questioned whether they can be involved in atherogenic processes. Exosomes isolated from the supernatants of activated human CD4 þ T lymphocytes induce cholesterol accumulation into monocytes subsequent to exosome internalization via the phosphatidylserine receptor [39]. Lipid droplets found in exosome-treated monocytes contained free cholesterol but also cholesterol esters. "
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    ABSTRACT: Dysregulation of lipid metabolism involves cellular communication mediated by cell contacts or exchange of bioactive lipids bound to soluble carriers or to lipoproteins. An increasing field is that of cellular communication mediated by nanovesicles called exosomes. Those vesicles are released from an internal compartment of viable cells, circulate in all biological fluids and can transfer material from cell-to-cells. Involvement of exosome trafficking in the transcellular metabolism of eicosanoids and cholesterol-related diseases including cancer is developed hereafter.
    Biochimie 07/2013; 96(1). DOI:10.1016/j.biochi.2013.06.016 · 2.96 Impact Factor
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    • "Presenting variable pattern specific to the parental cell, functional molecules including proteins, soluble factors, mRNAs, and miRNAs are enclosed inside exosomes or on their membrane (de Gassart et al., 2004; Chavez-Munoz et al., 2009; Mathivanan et al., 2010; Zhang et al., 2011). Recent studies have shown exosomes can attach to cell surface or enter into recipient cells (Zakharova et al., 2007; Thery et al., 2009; Zhang et al., 2009). Through the interaction between exosomes and their target cells, exosomes can transfer information between cells as a carrier (Gyorgy et al., 2011; Simons and Raposo, 2009). "
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    ABSTRACT: Cells release exosomes into extracellular medium. Although the important roles of exosomes in many physiological and pathological processes are being revealed, the mechanism of exosome-cell interaction remains unclear. In this paper, employing real-time fluorescence microscopy, the motion of exosomes on the plasma membrane or in the cytoplasm of recipient PC12 cells was observed directly. In addition, several motion modes of exosomes were revealed by single particle tracking (SPT). The changes between motion modes were also detected, presenting the dynamic courses of exosome attachment onto plasma membrane and exosome uptake. Octadecyl rhodamine B chloride (R18) was found to be useful to distinguish endocytosis from fusion during exosome uptake. Colocalization with organelle markers showed exosomes were sorted to acidic vesicles after internalization. The results provide new sight into the exosome-cell interaction mode and the intercellular trafficking of exosomes. This study will help to understand the roles of exosomes at cell level. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
    Journal of Cellular Physiology 07/2013; 228(7). DOI:10.1002/jcp.24304 · 3.84 Impact Factor
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